Gene Detail

Gene Symbol BRCA1
Synonyms BRCAI | BRCC1 | BROVCA1 | FANCS | IRIS | PNCA4 | PPP1R53 | PSCP | RNF53
Gene Description BRCA1 is a tumor suppressor involved in the DNA damage response and DNA repair (PMID: 21203981). BRCA1 germline mutations increase the risk of developing ovarian and/or breast cancer (PMID: 21285145) and somatic mutations are highest in NSCLC, pancreatic, and colon cancers (PMID: 27283171).
ACMG Incidental List v2.0:
Yes, Breast-ovarian cancer, familial 1 (PMID: 27854360)
Entrez Id 672
Chromosome 17
Map Location 17q21.31
Canonical Transcript NM_007294

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
M1008I missense no effect - predicted BRCA1 M1008I does not lie within any known functional domains of the Brca1 protein (UniProt.org). M1008I restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
L269V missense unknown BRCA1 L269V does not lie within any known functional domains of the Brca1 protein (UniProt.org). L269V has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
A1830T missense no effect BRCA1 A1830T lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1830T results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
K991Q missense unknown BRCA1 K991Q lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). K991Q has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L30F missense no effect - predicted BRCA1 L30F lies within the RING domain of the Brca1 protein (PMID: 22737296). L30F demonstrates homologous DNA repair activity at a similar level to wild-type Brca1 in culture (PMID: 25823446).
I90T missense no effect - predicted BRCA1 I90T does not lie within any known functional domains of the Brca1 protein (UniProt.org). I90T demonstrates binding to Bard1 and E2 at levels similar to that of wild-type Brca1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to have no effect on Brca1 protein function.
I31M missense loss of function - predicted BRCA1 I31M lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). I31M results in impaired centrosome duplication in cell culture (PMID: 21725363) and therefore, is predicted to result in a loss of Brca1 protein function.
R866C missense no effect - predicted BRCA1 R866C does not lie within any known functional domains of the Brca1 protein (UniProt.org). R866C restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
L1407P missense loss of function BRCA1 L1407P does not lie within any known functional domains of the Brca1 protein (UniProt.org). L1407P results in a loss of Brca1 transcription activity in yeast (PMID: 15689452) and leads to impaired binding of Palb2 and reduced homologous recombination activity in in vitro assays (PMID: 28398198).
E1258D missense unknown BRCA1 E1258D does not lie within any known functional domains of the Brca1 protein (Uniprot.org). E1258D has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E515V missense unknown BRCA1 E515V lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). E515V has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
F1695L missense no effect - predicted BRCA1 F1695L lies within the BRCT1 domain of the Brca1 protein (UniProt.org). F1695L demonstrates BRCT binding similar to wild-type Brca1 protein in an in vitro assay (PMID: 15133503) and therefore, is predicted to have no effect on Brca1 protein function.
V191I missense no effect - predicted BRCA1 V191I does not lie within any known functional domains of the Brca1 protein (UniProt.org). V191I restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to result in a loss of Brca1 protein function.
V1838E missense loss of function BRCA1 V1838E lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1838E results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
M1775K missense loss of function BRCA1 M1775K lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1775K results in defective BRCT binding and decreased Brca1 transcription activity in cell culture (PMID: 20516115, PMID: 18285836).
D1733G missense no effect BRCA1 D1733G lies within the BRCT1 domain of the Brca1 protein (UniProt.org). D1733G results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
M1663K missense no effect BRCA1 M1663K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1663K demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
G1763V missense loss of function BRCA1 G1763V lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). G1763V results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
Y1853C missense loss of function BRCA1 Y1853C lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). Y1853C results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
K38Sfs*12 frameshift loss of function - predicted BRCA1 K38Sfs*12 indicates a shift in the reading frame starting at amino acid 38 and terminating 12 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), K38Sfs*12 is predicted to result in a loss of Brca1 protein function; however, the corresponding cDNA change has been demonstrated to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by induction of Brca1 foci formation following ionizing irradiation in vitro and association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
S1566G missense unknown BRCA1 S1566G does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1566G has been identified in the scientific literature (PMID: 29880898), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
K996Q missense unknown BRCA1 K996Q lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). K996Q has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1512I missense no effect - predicted BRCA1 S1512I does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1512I demonstrates transcription activity similar to wild-type Brca1 in yeast (PMID: 15689452) and therefore, is predicted to have no effect on Brca1 protein function.
A1752V missense loss of function BRCA1 A1752V does not lie within any known functional domains of the Brca1 protein (UniProt.org). A1752V results in defective Brca1 protein folding and decreased transcription activity in cell culture (PMID: 20516115).
K1207N missense unknown BRCA1 K1207N does not lie within any known functional domains of the Brca1 protein (UniProt.org). K1207N has been identified in the scientific literature (PMID: 14722926), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L1854P missense unknown BRCA1 L1854P lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). L1854P has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
P1856T missense loss of function - predicted BRCA1 P1856T does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1856T results in a loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
V627I missense unknown BRCA1 V627I lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). V627I has been identified in the scientific literature (PMID: 23333482, PMID: 18559594, PMID: 15235020), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
A1789S missense no effect BRCA1 A1789S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1789S results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
L1795Pfs*3 frameshift loss of function BRCA1 L1795Pfs*3 (also referred to as BRCA1 5382insC) indicates a shift in the reading frame starting at amino acid 1795 and terminating 3 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). L1795Pfs*3 confers a loss of function to Brca1 protein as indicated by embryonic lethality in homozygous transgenic mouse models and tumorigenesis in heterozygous transgenic mouse models (PMID: 27454287).
K1183R missense unknown BRCA1 K1183R lies within the serine cluster domain of the Brca1 protein (PMID: 22737296). K1183R has been identified in the scientific literature (PMID: 17341484, PMID: 24600974, PMID: 28398198), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
D1123Y missense unknown BRCA1 D1123Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1123Y has not been characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
C27A missense loss of function BRCA1 C27A lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C27A confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
K1109T missense unknown BRCA1 K1109T does not lie within any known functional domains of the Brca1 protein (UniProt.org). K1109T has been identified in sequencing studies (PMID: 24816253), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
R1753T missense loss of function BRCA1 R1753T does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1753T results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
V1736A missense loss of function BRCA1 V1736A lies within the BRCT1 domain of the Brca1 protein (UniProt.org). V1736A results in defective Brca1 protein folding and decreased transcription activity in cell culture (PMID: 20516115).
S1448G missense no effect - predicted BRCA1 S1448G does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1448G restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to result in a loss of Brca1 protein function.
I1318Lfs*7 frameshift loss of function - predicted BRCA1 I1318Lfs*7 indicates a shift in the reading frame starting at amino acid 1318 and terminating 7 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), I1318Lfs*7 is predicted to result in a loss of Brca1 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, potentially leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
T1720I missense no effect - predicted BRCA1 T1720I lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1720I results in colony size similar to wild-type Brca1 in yeast (PMID: 15004537) and therefore, is predicted to have no effect on Brca1 protein function.
M1652T missense no effect BRCA1 M1652T lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1652T demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
G1788D missense loss of function - predicted BRCA1 G1788D lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). G1788D results in decreased Brca1 transcription activity in cell culture (PMID: 17308087) and therefore, is predicted to result in a loss of Brca1 protein function.
H513Y missense unknown BRCA1 H513Y lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). H513Y has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
F1761S missense loss of function - predicted BRCA1 F1761S lies within the BRCT2 domain of the Brca1 protein (UniProt.org). F1761S results in a loss of Brca1 transcription activity in yeast (PMID: 10811118) and therefore, is predicted to result in a loss of Brca1 protein function.
M1775R missense loss of function BRCA1 M1775R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1775R results in defective BRCT binding and decreased Brca1 transcription activity in cell culture (PMID: 20516115) and demonstrated reduced cell growth compared to wild-type Brca1 protein following irradiation in cell culture (PMID: 10635334).
M1628T missense no effect BRCA1 M1628T does not lie within any known functional domains of the Brca1 protein (UniProt.org). M1628T demonstrates transcription activity similar to wild-type Brca1 in yeast (PMID: 15689452, PMID: 15350310).
L28P missense unknown BRCA1 L28P lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). L28P is predicted to disrupt contact with UbcH5a and prevent folding as determined by structural modeling (PMID: 16403807).
L63F missense loss of function BRCA1 L63F lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). L63F results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
D1778Y missense no effect BRCA1 D1778Y lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). D1778Y results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
E577* nonsense loss of function - predicted BRCA1 E577* results in a premature truncation of the Brca1 protein at amino acid 577 of 1863 (UniProt.org). E577* has not been characterized, however, other C-terminal deletion mutants downstream of E577 are inactivating (PMID: 16618730), thus E577* is predicted to lead to a loss of Brca1 protein function.
K45T missense loss of function BRCA1 K45T lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K45T results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
P798L missense no effect - predicted BRCA1 P798L does not lie within any known functional domains of the Brca1 protein (UniProt.org). P798L restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
Y105C missense unknown BRCA1 Y105C does not lie within any known functional domains of the Brca1 protein (UniProt.org). Y105C is conflicting, as it restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrates moderately reduced single-strand anneal repair activity as compared to wild-type Brca1 in an in vitro assay (PMID: 23161852).
D1739V missense loss of function BRCA1 D1739V does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1739V results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
N1730S missense no effect BRCA1 N1730S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). N1730S demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
I31T missense unknown BRCA1 I31T lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). I31T has not been characterized, but is predicted to disrupt the RING domain of Brca1 as determined by structural modeling (PMID: 16403807).
V1665M missense no effect - predicted BRCA1 V1665M lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1665M demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115) and therefore, is predicted to have no effect on Brca1 protein function.
G57R missense unknown BRCA1 G57R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). G57R has not been characterized, but may alter packing with E2 or within RING as determined by structural modeling (PMID: 16403807).
C39S missense loss of function - predicted BRCA1 C39S lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C39S results in weakened Brca1 binding to Bard1 in yeast (PMID: 16403807) and therefore, is predicted to result in a loss of Bard1 protein function.
Y179C missense loss of function - predicted BRCA1 Y179C does not lie within any known functional domains of the Brca1 protein (UniProt.org). Y179C confers a loss of function on Brca1 protein as indicated by defective DNA double strand break repair by non-homologous end joining in cell culture (PMID: 20737206) and therefore, is predicted to result in a loss of Brca1 protein function.
C24Y missense unknown BRCA1 C24Y lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C24Y has not been characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
R1443* nonsense loss of function - predicted BRCA1 R1443* results in a premature truncation of the Brca1 protein at amino acid 1443 of 1863 (UniProt.org). R1443* has not been characterized, however, other C-terminal deletion mutants downstream of R1443 are inactivating (PMID: 16618730), thus R1443* is predicted to lead to a loss of Brca1 protein function.
C1697R missense loss of function BRCA1 C1697R lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). C1697R results in defective Brca1 protein folding and decreased transcription activity in cell culture (PMID: 20516115).
G1384W missense unknown BRCA1 G1384W lies within the serine cluster domain and the coiled-coil domain of the Brca1 protein (PMID: 22737296). G1384W has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
G1743R missense loss of function - predicted BRCA1 G1743R does not lie within any known functional domains of the Brca1 protein (UniProt.org). G1743R results in a loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
S4F missense unknown BRCA1 S4F does not lie within any known functional domains of the Brca1 protein (UniProt.org). S4F demonstrates variable effects on cisplatin sensitivity in cell culture (PMID: 23867111), and therefore its effect on Brca1 protein function is unknown.
P1812R missense no effect - predicted BRCA1 P1812R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1812R restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
V1653M missense loss of function BRCA1 V1653M lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1653M results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
S308A missense unknown BRCA1 S308A does not lie within any known functional domains of the Brca1 protein (UniProt.org). S308A is conflicting, as it restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrated impairment in the differentiation of embryonic stem cells in culture (PMID: 19770520).
E907K missense unknown BRCA1 E907K lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). E907K has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
V1808A missense no effect BRCA1 V1808A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1808A demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
R1835P missense unknown BRCA1 R1835P lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). R1835P results in impaired binding to BRCT, but demonstrated transcription activity similar to wild-type Brca1 in cell culture (PMID: 20516115).
P871L missense unknown BRCA1 P871L lies within the Rad51-binding region of the Brca1 protein (UniProt.org). P871L is a common Brca1 polymorphism (PMID: 14555511), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
V1714G missense loss of function BRCA1 V1714G lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1714G results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
S1655fs frameshift loss of function - predicted BRCA1 S1655fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 1655 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). S1655fs has not been characterized, however, other BRCT domain deletion mutants downstream of S1655 are destablizing (PMID: 14534301), thus, S1655fs is predicted to lead to a loss of Brca1 protein function.
C44Y missense unknown BRCA1 C44Y lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C44Y has not been biochemically characterized, but is considered deleterious to Brca1 protein function based on a predictive algorithm, suggesting loss of ubiquitin protein ligase E3 (E3) activity (PMID: 19543972).
R1726G missense no effect BRCA1 R1726G lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). R1726G demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
S1613C missense unknown BRCA1 S1613C does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1613C is conflicting as it demonstrates transcription activity similar to wild-type Brca1 protein in cell culture in one study (PMID: 18992264), but resulted in impaired transcription activity in another study (PMID: 9326340).
A1843P missense loss of function BRCA1 A1843P lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1843P results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
Q1409L missense no effect - predicted BRCA1 Q1409L does not lie within any known functional domains of the Brca1 protein (UniProt.org). Q1409L demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 23613828) and therefore, is predicted to have no effect on Brca1 protein function.
P1771L missense loss of function BRCA1 P1771L lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1771L results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
V1810G missense loss of function - predicted BRCA1 V1810G lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1810G results in decreased Brca1 transcription activity in cell culture (PMID: 20516115) and therefore, is predicted to result in a loss of Brca1 protein function.
W1718L missense loss of function - predicted BRCA1 W1718L lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). W1718L results in a loss of Brca1 transcription activity in cell culture (PMID: 23613828) and therefore, is predicted to result in a loss of Brca1 protein function.
G1706E missense loss of function BRCA1 G1706E lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). G1706E results in defective Brca1 protein folding and BRCT binding, and is predicted to disrupt Brca1 protein function (PMID: 20516115).
D435Y missense unknown BRCA1 D435Y lies within the Rad50-binding and MB1 binding region of the Brca1 protein (PMID: 22737296). D435Y has been identified in the scientific literature (PMID: 28857155), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1411T missense unknown BRCA1 M1411T does not lie within any known functional domains of the Brca1 protein (UniProt.org). M1411T restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrated an inability to restore gene conversion function in Brca1-depleted cells in culture (PMID: 19369211).
M18K missense loss of function BRCA1 M18K does not lie within any known functional domains of the Brca1 protein (UniProt.org). M18K results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
R1751P missense loss of function BRCA1 R1751P does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1751P results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
F461C missense unknown BRCA1 F461C lies within the Rad50-binding region and the MB1-binding region of the Brca1 protein (PMID: 22737296). F461C has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1101N missense no effect BRCA1 S1101N does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1101N restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and demonstrated single strand annealing activity similar to wild-type Brca1 in an in vitro assay (PMID: 28398198).
E851G missense unknown BRCA1 E851G lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). E851G has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
N1647K missense no effect BRCA1 N1647K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). N1647K demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
Q202* nonsense loss of function - predicted BRCA1 Q202* results in a premature truncation of the Brca1 protein at amino acid 202 of 1863 (UniProt.org). Q202* has not been characterized, however, other C-terminal deletion mutants downstream of Q202 are inactivating (PMID: 16618730), thus Q202* is predicted to lead to a loss of Brca1 protein function.
H619N missense unknown BRCA1 H619N lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). H619N has been identified in sequencing studies (PMID: 30404001), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
V191D missense unknown BRCA1 V191D does not lie within any known functional domains of the Brca1 protein (UniProt.org). V191D is conflicting, as it repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but demonstrates reduced activity by the single-strand annealing pathway in cell culture (PMID: 23161852).
C39R missense loss of function BRCA1 C39R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C39R results in impaired Brca1 binding to E2 and loss of E3 ligase activity in yeast (PMID: 16403807).
E1682K missense no effect BRCA1 E1682K lies within the BRCT1 domain of the Brca1 protein (UniProt.org). E1682K results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
T1852S missense unknown BRCA1 T1852S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). T1852S has been identified in sequencing studies (PMID: 15172985), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
K1254T missense unknown BRCA1 K1254T does not lie within any known functional domains of the Brca1 protein (UniProt.org). K1254T has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
K45N missense loss of function BRCA1 K45N lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K45N results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
P1812S missense unknown BRCA1 P1812S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1812S has been identified in sequencing studies (PMID: 17719744, PMID: 15172985), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
V899L missense unknown BRCA1 V899L lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). V899L has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
F1704S missense loss of function - predicted BRCA1 F1704S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). F1704S results in a loss of Brca1 transcription activity in yeast (PMID: 15004537) and therefore, is predicted to result in a loss of Brca1 protein function.
H1862L missense no effect - predicted BRCA1 H1862L does not lie within any known functional domains of the Brca1 protein (UniProt.org). H1862L restores proliferation of Brca1-null embryonic stem cells to a level similar to wild-type Brca1 in culture (PMID: 23867111) and therefore, is predicted have no effect on Brca1 protein function.
M1783L missense no effect BRCA1 M1783L lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1783L demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
A942V missense unknown BRCA1 A942V lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). A942V has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
K38N missense no effect - predicted BRCA1 K38N lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K38N demonstrates binding to Bard1 and E2 at levels similar to that of wild-type Brca1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to have no effect on Brca1 protein function.
N550H missense no effect - predicted BRCA1 N550H does not lie within any known functional domains of the Brca1 protein (UniProt.org). N550H results in DNA double strand break repair by non-homologous end joining to similar level of wild-type Brca1 protein in cell culture (PMID: 20737206) and therefore, is predicted to have no effect on Brca1 protein function.
Q1811R missense loss of function BRCA1 Q1811R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). Q1811R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
H1402Y missense no effect - predicted BRCA1 H1402Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). H1402Y demonstrates transcription activity similar to wild-type Brca1 in yeast (PMID: 15689452) and therefore, is predicted to have no effect on Brca1 protein function.
Q356R missense loss of function BRCA1 Q356R lies within the ZBRK1-binding region of the Brca1 protein (PMID: 11090615). Q356R interferes with binding of Brca1 to Zbrk1, resulting in decreased Brca1-dependent repression activity of Zbrk1, and interferes with repression of ligand-independent ER-alpha transcriptional activation in cell culture (PMID: 11090615, PMID: 11493692).
E1794D missense no effect BRCA1 E1794D lies within the BRCT2 domain of the Brca1 protein (UniProt.org). E1794D results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
W1718C missense loss of function BRCA1 W1718C lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). W1718C results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
P1776S missense unknown BRCA1 P1776S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1776S has been identified in the scientific literature (PMID: 10196379, PMID: 15172985), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1715N missense loss of function BRCA1 S1715N lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1715N results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
C47W missense unknown BRCA1 C47W lies within the RING-type Zinc finger region of the Brca1 protein (UniProt.org). C47W has been identified in the scientific literature (PMID: 23232854), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1? missense loss of function - predicted BRCA1 M1? indicates a disruption of the methionine (M) start codon with an unknown translational effect on the Brca1 protein. M1? has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Jun 2016).
D1818G missense no effect BRCA1 D1818G lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). D1818G results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
H1746N missense loss of function BRCA1 H1746N does not lie within any known functional domains of the Brca1 protein (UniProt.org). H1746N results in defective Brca1 protein folding and BRCT binding, and moderately decreased transcription activity in cell culture (PMID: 20516115).
G275D missense unknown BRCA1 G275D does not lie within any known functional domains of the Brca1 protein (UniProt.org). G275D has been identified in the scientific literature (PMID: 29601120), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E1419K missense unknown BRCA1 E1419K lies within the PALB2-interacting region of the Brca1 protein (UniProt.org). E1419K has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
D821Y missense unknown BRCA1 D821Y lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). D821Y has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
mutant unknown unknown BRCA1 mutant indicates an unspecified mutation in the BRCA1 gene.
A622V missense unknown BRCA1 A622V lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). A622V has been identified in sequencing studies (PMID: 20104584, PMID: 17924331), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
R1751Q missense no effect BRCA1 R1751Q does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1751Q demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
V1590A missense unknown BRCA1 V1590A does not lie within any known functional domains of the Brca1 protein (UniProt.org). V1590A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
G1803A missense loss of function - predicted BRCA1 G1803A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). G1803A results in decreased Brca1 transcription activity in cell culture (PMID: 20516115) and therefore, is predicted to result in a loss of Brca1 protein function.
S1651F missense no effect BRCA1 S1651F lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1651F demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
S1715C missense loss of function - predicted BRCA1 S1715C lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1715C results in decreased Brca1 transcription activity in cell culture (PMID: 20516115) and therefore, is predicted to result in a loss of Brca1 protein function.
D1344H missense unknown BRCA1 D1344H does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1344H has been identified in sequencing studies (PMID: 25416589), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
V1714A missense unknown BRCA1 V1714A lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1714A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1164G missense unknown BRCA1 S1164G lies within the MSH2-interacting region of the Brca1 protein (PMID: 24832651). S1164G has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L1657P missense loss of function - predicted BRCA1 L1657P lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). L1657P results in a loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
E515G missense unknown BRCA1 E515G lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). E515G has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
G1706A missense no effect BRCA1 G1706A lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). G1706A results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
G1738R missense loss of function BRCA1 G1738R does not lie within any known functional domains of the Brca1 protein (UniProt.org). G1738R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
E515Q missense unknown BRCA1 E515Q lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). E515Q has been identified in sequencing studies (PMID: 25855536), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
T1685A missense loss of function BRCA1 T1685A lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1685A results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
D1778H missense unknown BRCA1 D1778H lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). D1778H has been identified in the scientific literature (PMID: 15172985), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
A1752P missense loss of function BRCA1 A1752P does not lie within any known functional domains of the Brca1 protein (UniProt.org). A1752P results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
K1702E missense loss of function - predicted BRCA1 K1702E lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). K1702E is predicted to confer a loss of function to the Brca1 protein as indicated by decreased transcription activation in a yeast-based assay (PMID: 10811118).
M1628V missense no effect - predicted BRCA1 M1628V does not lie within any known functional domains of the Brca1 protein (UniProt.org). M1628V demonstrates transcription activity similar to wild-type Brca1 protein in vitro (PMID: 17311832) and therefore, is predicted to have no effect on Brca1 protein function.
G1738E missense loss of function BRCA1 G1738E does not lie within any known functional domains of the Brca1 protein (UniProt.org). G1738E results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
F1761I missense loss of function - predicted BRCA1 F1761I lies within the BRCT2 domain of the Brca1 protein (UniProt.org). F1761I results in a loss of Brca1 transcription activity in yeast (PMID: 10811118) and therefore, is predicted to result in a loss of Brca1 protein function.
M18T missense loss of function BRCA1 M18T does not lie within any known functional domains of the Brca1 protein (UniProt.org). M18T confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
I21V missense unknown BRCA1 I21V does not lie within any known functional domains of the Brca1 protein (UniProt.org). I21V is conflicting as it impaired centrosome duplication in cell culture (PMID: 21725363), but restored homologous recombination to a level similar to wild-type Brca1 in culture (PMID: 21372787).
T231M missense no effect - predicted BRCA1 T231M does not lie within any known functional domains of the Brca1 protein (UniProt.org). T231M restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111).
Q1785H missense no effect BRCA1 Q1785H lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). Q1785H demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in mammalian cell culture and yeast (PMID: 20516115, PMID: 17308087).
L1844R missense loss of function BRCA1 L1844R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). L1844R results in defective Brca1 protein folding and BRCT binding, and moderately decreased transcription activity in cell culture (PMID: 20516115).
W1782* nonsense loss of function - predicted BRCA1 W1782* results in a premature truncation of the Brca1 protein at amino acid 1782 of 1863 (UniProt.org). W1782* has not been characterized, however, other BRCT domain deletion mutants downstream of W1782 are destablizing (PMID: 14534301), thus W1782* is predicted to lead to a loss of Brca1 protein function.
E1836K missense unknown BRCA1 E1836K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). The functional effect of E1836K is conflicting, as E1836K has been reported to confer minimal reduction in binding affinity compared to wild-type in vitro (PMID: 21473589), and maintains homology directed repair similar to wild-type in cell lines (PMID: 30257991), but is also reported to confer compromised binding activity, compromised binding specificity, and unclear transcription activity in vitro (PMID: 20516115), and therefore, its effect on Brca1 protein function is unknown.
P1812A missense no effect - predicted BRCA1 P1812A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1812A demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 17020472) and therefore, is predicted to have no effect on Brca1 protein function.
M1775V missense no effect - predicted BRCA1 M1775V lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1775V results in transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 8942979) and therefore, is predicted to have no effect on Brca1 protein function.
W321C missense unknown BRCA1 W321C lies within the RB-binding region of the Brca1 protein (PMID: 22737296). W321C has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E143K missense unknown BRCA1 E143K does not lie within any known functional domains of the Brca1 protein (UniProt.org). E143K repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but with reduced activity by the single-strand annealing pathway in cell culture (PMID: 23161852) and demonstrated decreased Brca1 accumulation at double-strand breaks post irradiation treatment (PMID: 18936166).
Q1756* nonsense loss of function - predicted BRCA1 Q1756* results in a premature truncation of the Brca1 protein at amino acid 1756 of 1863 (UniProt.org). Q1756* has not been characterized, however, other BRCT domain deletion mutants downstream of Q1756 are destablizing (PMID: 14534301), thus Q1756* is predicted to lead to a loss of Brca1 protein function.
Q1299L missense unknown BRCA1 Q1299L lies within the serine cluster domain of the Brca1 protein (PMID: 22737296). Q1299L has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E1214K missense no effect - predicted BRCA1 E1214K does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1214K restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
G1656D missense no effect - predicted BRCA1 G1656D lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). G1656D demonstrates peptide binding affinity similar to wild-type Brca1 protein (PMID: 21473589) and therefore, is predicted to have no effect on Brca1 protein function.
D1692H missense loss of function - predicted BRCA1 D1692H lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). D1692H results in decreased Brca1 transcription activity in cell culture (PMID: 20516115) and therefore, is predicted to result in a loss of Brca1 protein function.
C644W missense unknown BRCA1 C644W lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). C644W has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L1664P missense no effect BRCA1 L1664P lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). L1664P demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
S1294G missense unknown BRCA1 S1294G does not lie within any known function domains in the Brca1 protein (UniProt.org). S1294G has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Jun 2018).
W1718S missense loss of function BRCA1 W1718S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). W1718S results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
P1859R missense no effect BRCA1 P1859R does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1859R demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
L52F missense unknown BRCA1 L52F lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). L52F is conflicting, as it demonstrates impaired centrosome duplication in cell culture (PMID: 21725363), but showed homology directed recombination and single strand annealing activity similar to wild-type Brca1 (PMID: 20103620).
R1589P missense no effect - predicted BRCA1 R1589P does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1589P restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
S1596Nfs*25 frameshift loss of function - predicted BRCA1 S1596Nfs*25 indicates a shift in the reading frame starting at 1596 and terminating 25 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). S1596Nfs*25 has not been characterized, however, other BRCT domain deletions downstream of S1596 are destabilizing (PMID: 14534301), thus S1596Nfs*25 is predicted to lead to a loss of Brca1 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, potentially leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
A1823T missense no effect BRCA1 A1823T lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1823T results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
E1060A missense no effect - predicted BRCA1 E1060A does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1060A restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
L1564P missense loss of function - predicted BRCA1 L1564P does not lie within any known functional domains of the Brca1 protein (UniProt.org). L1564P results in reduced Brca1 transcription activity in cell culture (PMID: 17308087) and therefore, is predicted to result in a loss of Brca1 protein function.
Q94* nonsense loss of function - predicted BRCA1 Q94* results in a premature truncation of the Brca1 protein at amino acid 94 of 1863 (UniProt.org). Due to the loss of most known functional domains (UniProt.org), Q94* is predicted to lead to a loss of Brca1 protein function.
W1837G missense loss of function BRCA1 W1837G lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). W1837G results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
K339fs frameshift loss of function - predicted BRCA1 K339fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 339 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). K339fs has not been characterized, however, C-terminal deletion mutants downstream of K339 are inactivating (PMID: 16618730), thus K339fs is predicted to lead to a loss of Brca1 protein function.
E23fs frameshift loss of function - predicted BRCA1 E23fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 23 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), E23fs is predicted to lead to a loss of Brca1 function.
S1512A missense unknown BRCA1 S1512A lies within MSH2-interacting region of the Brca1 protein (PMID: 24832651). S1512A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
dec exp none no effect BRCA1 dec exp indicates decreased expression of the Brca1 protein and/or mRNA. However, the mechanism causing the decreased expression is unspecified.
P1749R missense loss of function BRCA1 P1749R does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1749R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115), and demonstrates impaired function to repair double-strand breaks as efficiently as wild-type Brca1 in culture (PMID: 10635334).
W1837C missense loss of function BRCA1 W1837C lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). W1837C results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
del deletion loss of function BRCA1 del indicates a deletion of the BRCA1 gene.
T1700A missense loss of function BRCA1 T1700A lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1700A results in defective Brca1 binding to BRCT and decreased transcription activity in cell culture (PMID: 20516115).
D1739G missense loss of function BRCA1 D1739G does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1739G results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
T1393A missense unknown BRCA1 T1393A lies within the coiled-coil domain of the Brca1 protein (PMID: 22737296). T1393A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L49M missense no effect - predicted BRCA1 L49M lies within the RING domain of the Brca1 protein (PMID: 22737296). L49M demonstrates homologous DNA repair activity at a similar level to wild-type Brca1 in culture (PMID: 25823446).
negative unknown loss of function BRCA1 negative indicates a lack of the BRCA1 gene, mRNA, and/or protein.
L165P missense no effect - predicted BRCA1 L165P does not lie within any known functional domains of the Brca1 protein (UniProt.org). L165P restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
C1787S missense no effect BRCA1 C1787S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). C1787S results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
L1705P missense loss of function - predicted BRCA1 L1705P lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). L1705P results in a loss of Brca1 transcription activity in yeast (PMID: 10811118) and therefore, is predicted to result in a loss of Brca1 protein function.
I124V missense unknown BRCA1 I124V does not lie within any known functional domains of the Brca1 protein (UniProt.org). I124V repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but with reduced activity by the single-strand annealing pathway in cell culture (PMID: 23161852), and therefore its effect on Brca1 protein function is unknown.
C64G missense loss of function - predicted BRCA1 C64G lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C64G is predicted to confer a loss of function to the Brca1 protein as indicated by failure to repair DNA double strand break in cell culture (PMID: 10635334).
I89T missense no effect - predicted BRCA1 I89T does not lie within any known functional domains of the Brca1 protein (UniProt.org). I89T demonstrates binding to Bard1 and E2 at levels similar to that of wild-type Brca1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to have no effect on Brca1 protein function.
P142H missense unknown BRCA1 P142H does not lie within any known functional domains of the Brca1 protein (UniProt.org). P142H is conflicting as it restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrated moderately reduced single strand annealing repair activity as compared to wild-type Brca1 in vitro (PMID: 23161852) and resulted in an inability to restore Brca1 repair activity in BRCA1-deficient cells in culture (PMID: 18936166).
L1267S missense no effect - predicted BRCA1 L1267S does not lie within any known functional domains of the Brca1 protein (UniProt.org). L1267S restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
A1843T missense loss of function - predicted BRCA1 A1843T lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1843T results in a loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
D1692N missense unknown BRCA1 D1692N lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). D1692N results in BRCT binding and transactivation similar to wild-type Brca1 protein in cell culture (PMID: 20516115, PMID: 11157798), but may introduce a deleterious splice junction effect (PMID: 17305420).
S186Y missense no effect - predicted BRCA1 S186Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). S186Y restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
E427_S713del deletion unknown BRCA1 E427_S713del results in the deletion of 287 amino acids in the Brca1 protein (UniProt.org). E427_S713del has been identified in the scientific literature (PMID: 28588062), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Aug 2018).
R170W missense no effect - predicted BRCA1 R170W does not lie within any known functional domains of the Brca1 protein (UniProt.org). R170W restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
Q1826H missense no effect - predicted BRCA1 Q1826H lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). Q1826H demonstrates transcription activity similar to wild-type Brca1 protein in mammalian cell culture and yeast (PMID: 18992264) and therefore, is predicted to have no effect on Brca1 protein function.
L1570P missense unknown BRCA1 L1570P does not lie within any known functional domains of the Brca1 protein (UniProt.org). L1570P has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S988A missense unknown BRCA1 S988A does not lie within any known functional domains of the Brca1 protein (UniProt.org). S988A is conflicting, as it restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrates impaired homologous recombination activity compared to wild-type Brca1 (PMID: 14701743).
C44F missense loss of function BRCA1 C44F lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C44F confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
A1789T missense loss of function BRCA1 A1789T lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). A1789T results in dysregulation of expression of genes controlling cell cycle and genome integrity (PMID: 22646717) and leads to altered non-homologous end-joining activity as compared to wild-type Brca1 (PMID: 20737206).
S1027I missense unknown BRCA1 S1027I lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). S1027I has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
A314T missense unknown BRCA1 A314T lies within the RB-binding region of the Brca1 protein (PMID: 22737296). A314T has not been characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E1258G missense unknown BRCA1 E1258G does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1258G has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
N1309Ifs*9 frameshift loss of function - predicted BRCA1 N1309Ifs*9 indicates a shift in the reading frame starting at amino acid 1309 and terminating 9 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), N1309Ifs*9 is predicted to result in a loss of Brca1 protein function; however, the corresponding cDNA change has been predicted to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, potentially leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
R1589C missense unknown BRCA1 R1589C does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1589C has been identified in sequencing studies (PMID: 29349598), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S4P missense no effect - predicted BRCA1 S4P does not lie within any known functional domains of the Brca1 protein (UniProt.org). S4P demonstrates binding to Bard1 and E2 to similar levels of wild-type Brca1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to have no effect on Brca1 protein function.
L147F missense no effect - predicted BRCA1 L147F does not lie within any known functional domains of the Brca1 protein (UniProt.org). L147F restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
S1297del deletion no effect - predicted BRCA1 S1297del results in the deletion of one amino acid of the Brca1 protein at amino acid 1297 (UniProt.org). S1297del restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to result in a loss of Brca1 protein function.
K654fs frameshift loss of function - predicted BRCA1 K654fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 654 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). K654fs has not been characterized, however, C-terminal deletion mutants downstream of K654 are inactivating (PMID: 16618730), thus K654fs is predicted to lead to a loss of Brca1 protein function.
L1764P missense loss of function BRCA1 L1764P lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). L1764P results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
L1780P missense loss of function BRCA1 L1780P lies within the BRCT2 domain of the Brca1 protein (UniProt.org). L1780P results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
F1662S missense no effect BRCA1 F1662S lies within the BRCT1 domain of the Brca1 protein (UniProt.org). F1662S results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
N1819Y missense no effect - predicted BRCA1 N1819Y lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). N1819Y results in colony size similar to wild-type Brca1 in yeast (PMID: 15004537) and therefore, is predicted to have no effect on Brca1 protein function.
M1652I missense no effect BRCA1 M1652I lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1652I demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 18992264) and showed complete rescue of lethality in Brca1-null mouse models (PMID: 19770520).
Y856H missense no effect - predicted BRCA1 Y856H does not lie within any known functional domains of the Brca1 protein (UniProt.org). Y856H restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
G1770V missense loss of function - predicted BRCA1 G1770V lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). G1770V results in a loss of Brca1 transcription activity in cell culture (PMID: 23613828) and therefore, is predicted to result in a loss of Brca1 protein function.
D695N missense no effect - predicted BRCA1 D695N does not lie within any known functional domains of the Brca1 protein (UniProt.org). D695N restores proliferation levels similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
R1443G missense loss of function - predicted BRCA1 R1443G does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1443G results in reduced Brca1 transcription activity in cell culture (PMID: 17308087) and therefore, is predicted to result in a loss of Brca1 protein function.
S1040N missense unknown BRCA1 S1040N lies within the RAD51-interacting domain of the Brca1 protein (PMID: 24832651). S1040N has been identified in sequencing studies (PMID: 24793135, PMID: 11389159), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1211F missense unknown BRCA1 S1211F does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1211F has not been characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S561Y missense unknown BRCA1 S561Y lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). S561Y has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
R841Q missense no effect - predicted BRCA1 R841Q does not lie within any known functional domains of the Brca1 protein (UniProt.org). R841Q restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
W1837R missense loss of function BRCA1 W1837R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). W1837R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
S1503* nonsense loss of function - predicted BRCA1 S1503* results in a premature truncation of the Brca1 protein at amino acid 1503 of 1863 (UniProt.org). S1503* has not been characterized, however, other C-terminal deletion mutants downstream of S1503 are inactivating (PMID: 16618730), thus S1503* is predicted to lead to a loss of Brca1 protein function.
L574I missense unknown BRCA1 L574I lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). L574I has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
H1686Q missense loss of function - predicted BRCA1 H1686Q lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). H1686Q results in a temperature-sensitive loss of Brca1 transcription activity (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
D245V missense no effect - predicted BRCA1 D245V does not lie within any known functional domains of the Brca1 protein (UniProt.org). D245V restores proliferation at a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
inact mut unknown loss of function BRCA1 inact mut indicates that this variant results in a loss of function of the Brca1 protein. However, the specific amino acid change has not been identified.
S59R missense loss of function - predicted BRCA1 S59R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). S59R results in a loss of Brca1 binding to E2 in an in vitro assay (PMID: 16403807) and therefore, is predicted to result in a loss of Brca1 protein function.
V1534M missense no effect - predicted BRCA1 V1534M does not lie within any known functional domains of the Brca1 protein (UniProt.org). V1534M demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 17308087) and therefore, is predicted to have no effect on Brca1 protein function.
R841W missense no effect - predicted BRCA1 R841W lies within the Rad51 binding region of the Brca1 protein (PMID: 22737296). R841W maintains homology-directed repair similar to Brca1 wild-type in cell culture, and in a drug sensitivity assay, demonstrates colony growth similar to wild-type (PMID: 28398198), and therefore, is predicted to have no effect on Brca1 protein function.
R1203* nonsense loss of function - predicted BRCA1 R1203* results in a premature truncation of the Brca1 protein at amino acid 1203 of 1863 (UniProt.org). R1203* has not been characterized, however, other C-terminal deletion mutants downstream of R1203 are inactivating (PMID: 16618730), thus R1203* is predicted to lead to a loss of Brca1 protein function.
R133H missense unknown BRCA1 R133H does not lie within any known functional domains of the Brca1 protein (UniProt.org). R133H is conflicting, as it repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but demonstrates increased activity by the single-strand annealing pathway in cell culture (PMID: 23161852), and therefore, its effect on Brca1 protein function is unknown.
R320T missense unknown BRCA1 R320T lies within the RB-binding region of the Brca1 protein (PMID: 22737296). R320T has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
T1720A missense no effect BRCA1 T1720A lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1720A demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115, PMID: 15689452).
E962A missense unknown BRCA1 E962A lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). E962A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
L668F missense no effect BRCA1 L668F does not lie within any known functional domains of the Brca1 protein (UniProt.org). L668F restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and demonstrated single strand annealing activity levels similar to that of wild-type Brca1 protein in an in vitro assay (PMID: 28398198).
R1347G missense no effect - predicted BRCA1 R1347G lies within the serine cluster domain of the Brca1 protein (PMID: 22737296). R1347G maintains homology-directed repair similar to Brca1 wild-type in cell culture, and in a drug sensitivity assay, demonstrates colony growth similar to wild-type (PMID: 28398198), and therefore, is predicted to have no effect on Brca1 protein function.
T37Qfs*13 frameshift loss of function - predicted BRCA1 T37Qfs*13 indicates a shift in the reading frame starting at amino acid 37 and terminating 13 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), T37Qfs*13 is predicted to result in a loss of Brca1 protein function; however, the corresponding cDNA change has been demonstrated to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by induction of Brca1 foci formation following ionizing irradiation in vitro and association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
P1637L missense no effect - predicted BRCA1 P1637L does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1637L results in colony size similar to wild-type Brca1 in yeast (PMID: 15004537, PMID: 9159158) and therefore, is predicted to have no effect on Brca1 protein function.
K45Q missense no effect BRCA1 K45Q lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K45Q restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and did not result in a change in nuclear localization form as compared to wild-type Brca1 in culture when treated with DNA-damaging agents (PMID: 27484786).
D1739Y missense loss of function BRCA1 D1739Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1739Y results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
I15T missense unknown BRCA1 I15T does not lie within any known functional domains of the Brca1 protein (UniProt.org). I15T has not been characterized, but is predicted to prevent interaction with the E2 ubiquitin conjugating enzyme UbcH5a by structural modeling (PMID: 16403807).
D1344N missense unknown BRCA1 D1344N does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1344N has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1775E missense loss of function - predicted BRCA1 M1775E lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1775E results in decreased binding to core RNA polymerase II in an in vitro assay (PMID: 10725406) and therefore, is predicted to result in a loss of Brca1 protein function.
C360R missense unknown BRCA1 C360R lies within the RB-binding region and Rad50-binding region of the Brca1 protein (PMID: 22737296). C360R has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1655F missense loss of function BRCA1 S1655F lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1655F results in defective BRCT binding and decreased Brca1 transcription activity in cell culture (PMID: 20516115).
T1691I missense loss of function BRCA1 T1691I lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1691I results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
T826K missense loss of function - predicted BRCA1 T826K does not lie within any known functional domains of the Brca1 protein (UniProt.org). T826K results in failure to repair DNA double strand break in cell culture (PMID: 10635334) and therefore, is predicted to result in a loss of Brca1 protein function.
C1767S missense no effect - predicted BRCA1 C1767S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). C1767S has not been fully biochemically characterized, but results in cell growth levels similar to wild-type Brca1 in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
A1669S missense no effect BRCA1 A1669S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). A1669S results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
V1696L missense loss of function BRCA1 V1696L lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). V1696L results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
S1841A missense loss of function - predicted BRCA1 S1841A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). S1841A results in decreased Brca1 transcription activity in cell culture (PMID: 11016938) and therefore, is predicted to result in a loss of Brca1 protein function.
V271L missense no effect - predicted BRCA1 V271L does not lie within any known functional domains of the Brca1 protein (UniProt.org). V271L restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
V340* nonsense loss of function - predicted BRCA1 V340* results in a premature truncation of the Brca1 protein at amino acid 340 of 1863 (UniProt.org). Due to the loss of most major functional domains (UniProt.org), V340* is predicted to result in a loss of function (PMID: 8589721).
C39Y missense loss of function BRCA1 C39Y lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C39Y confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
K1487R missense loss of function - predicted BRCA1 K1487R does not lie within any known functional domains of the Brca1 protein (UniProt.org). K1487R results in reduced Brca1 transcription activity in cell culture (PMID: 18992264) and therefore, is predicted to result in a loss of Brca1 protein function.
E23Vfs*17 frameshift loss of function BRCA1 E23Vfs*17 (also referred to as BRCA1 185delAG) indicates a shift in the reading frame starting at amino acid 23 and terminating 17 residues downstream causing a premature truncation of the 1863 amino acid Brca1 protein (UniProt.org). E23Vfs*17 confers a loss of function to the Brca1 protein as indicated by embryonic lethality in homozygous transgenic mouse models and tumorigenesis in heterozygous transgenic mouse models (PMID: 27454287).
E1586G missense no effect - predicted BRCA1 E1586G does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1586G demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 23613828) and therefore, is predicted to have no effect on Brca1 protein function.
Q155E missense unknown BRCA1 Q155E does not lie within any known functional domains of the Brca1 protein (UniProt.org). Q155E has been identified in sequencing studies (PMID: 17924331), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
F79S missense unknown BRCA1 F79S does not lie within any known functional domains of the Brca1 protein (UniProt.org). F79S has not been biochemically characterized, but is predicted to change packing of the Brca1 RING-domain to helical domain by structural modeling (PMID: 16403807).
S1473P missense no effect - predicted BRCA1 S1473P does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1473P demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 23613828) and therefore, is predicted to have no effect on Brca1 protein function.
V1804D missense unknown BRCA1 V1804D lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1804D is conflicting, as it results in colony size similar to wild-type Brca1 in yeast (PMID: 15004537), but decreased transcriptional activity as compared to wild-type Brca1 in culture (PMID: 15350310).
E1038G missense no effect - predicted BRCA1 E1038G lies within the Rad51-binding domain of the Brca1 protein (PMID: 22737296). E1038G is a common Brca1 polymorphism (PMID: 23674270) and demonstrates homologous recombination activity similar to wild-type Brca1 protein (PMID: 28398198) and therefore, is predicted to have no effect on Brca1 protein function.
Y1703H missense loss of function - predicted BRCA1 Y1703H lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). Y1703H results in a loss of Brca1 transcription activity in yeast (PMID: 10811118) and therefore, is predicted to result in a loss of Brca1 protein function.
D1778G missense no effect BRCA1 D1778G lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). D1778G results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
V1804A missense no effect - predicted BRCA1 V1804A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1804A results in colony size similar to wild-type Brca1 in yeast (PMID: 15004537) and therefore, is predicted to have no effect on Brca1 protein function.
A1708E missense loss of function BRCA1 A1708E lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). A1708E results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
E404D missense unknown BRCA1 E404D lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). E404D has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E673* nonsense loss of function - predicted BRCA1 E673* results in a premature truncation of the Brca1 protein at amino acid 673 of 1863 (UniProt.org). E673* has not been characterized, however, other C-terminal deletion mutants downstream of E673 are inactivating (PMID: 16618730), thus E673* is predicted to lead to a loss of Brca1 protein function.
H1421Y missense no effect - predicted BRCA1 H1421Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). H1421Y demonstrates transcription activity similar to wild-type Brca1 in yeast (PMID: 15689452) and therefore, is predicted to have no effect on Brca1 protein function.
S1841R missense loss of function BRCA1 S1841R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). S1841R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
N1819S missense no effect BRCA1 N1819S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). N1819S demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
G1788V missense loss of function BRCA1 G1788V lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). G1788V results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
E1000Q missense unknown BRCA1 E1000Q lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). E1000Q has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E1660G missense loss of function - predicted BRCA1 E1660G lies within the BRCT1 domain of the Brca1 protein (UniProt.org). E1660G results in a loss of Brca1 transcription activity in yeast (PMID: 12496477).
A1752G missense loss of function BRCA1 A1752G does not lie within any known functional domains of the Brca1 protein (UniProt.org). A1752G results in decreased Brca1 transcription activity in cell culture (PMID: 23842040) and therefore, is predicted to result in a loss of Brca1 protein function.
E362H missense no effect - predicted BRCA1 E362H does not lie within any known functional domains of the Brca1 protein (UniProt.org). E362H restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
H1686R missense loss of function - predicted BRCA1 H1686R lies within the BRCT1 domain of the Brca1 protein (UniProt.org). H1686R results in failure to restore proliferation in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to result in a loss of Brca1 protein function.
S1164I missense loss of function - predicted BRCA1 S1164I does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1164I results in loss of growth suppression in yeast (PMID: 19493677) and therefore, is predicted to result in a loss of Brca1 protein function.
P1771R missense loss of function - predicted BRCA1 P1771R lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1771R results in moderate decrease of Brca1 transcription activity in cell culture (PMID: 20516115) and therefore is predicted to result in a loss of Brca1 protein function.
D853N missense unknown BRCA1 D853N lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). D853N has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1715R missense loss of function BRCA1 S1715R lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1715R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
C61G missense unknown BRCA1 C61G lies within the RING-type domain of the Brca1 protein (UniProt.org). C61G decreases Brca1 heterodimerization and leads to decreased Brca1/Bard1 E3 ubiquitin ligase activity, but may retain some residual Brca1 activity (PMID: 9525870, PMID: 22172724).
K50E missense unknown BRCA1 K50E lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K50E has not been characterized, but may disrupt the salt bridge to D59 of UbcH5b and weaken binding to E2 as determined by structural modeling (PMID: 16403807).
D1546N missense no effect - predicted BRCA1 D1546N does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1546N demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 17308087) and therefore, is predicted to have no effect on Brca1 protein function.
T77M missense loss of function BRCA1 T77M does not lie within any known functional domains of the Brca1 protein (UniProt.org). T77M results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
K65M missense unknown BRCA1 K65M lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K65M has not been characterized, but is predicted to disrupt hydrogen bonding or the salt bridge to UbcH5a as determined by structural modeling (PMID: 16403807).
F1734L missense loss of function - predicted BRCA1 F1734L lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). F1734L results in a temperature-sensitive loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
R1699Q missense loss of function - predicted BRCA1 R1699Q lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). R1699Q results in decreased Brca1 transcriptional activity in cultured cells (PMID: 11157798) and therefore, is predicted to result in a loss of Brca1 protein function.
K50L missense unknown BRCA1 K50L lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K50L has not been characterized, but may disrupt the salt bridge to D59 of UbcH5b and weaken binding to E2 as determined by structural modeling (PMID: 16403807).
D693N missense no effect - predicted BRCA1 D693N lies within the Rad50-binding domain of the Brca1 protein (PMID: 22737296). D693N is a common Brca1 polymorphism (PMID: 23674270), and maintains homology-directed repair activity similar to wild-type in cell lines (PMID: 28398198) and therefore, is predicted to have no effect on Brca1 protein function.
E1250K missense no effect - predicted BRCA1 E1250K does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1250K restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
Q1756C missense unknown BRCA1 Q1756C lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). Q1756C has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S72R missense loss of function BRCA1 S72R does not lie within any known functional domains of the Brca1 protein (UniProt.org). S72R results in a loss of E2 binding and Brca1 ubiquitin ligase activity in an in vitro assay (PMID: 16403807).
V1688del deletion loss of function BRCA1 V1688del results in the deletion of one amino acid of the Brca1 protein at amino acid 1688 (UniProt.org). V1688del results in failure to restore proliferation in Brca1-null embryonic stem cells in culture (PMID: 23867111), partially disrupts BRCT folding, leads to decreased stability, and demonstrates impaired DNA damage repair activity (PMID: 19706752).
D1851E missense no effect BRCA1 D1851E lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). D1851E results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
S1486C missense no effect - predicted BRCA1 S1486C does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1486C restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
wild-type none no effect BRCA1 wild-type indicates that no mutation has been detected within the BRCA1 gene.
M1689T missense loss of function BRCA1 M1689T lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1689T results in defective BRCT binding and moderately decreased Brca1 transcription activity in cell culture (PMID: 20516115).
S784L missense unknown BRCA1 S784L lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). S784L has been identified in the scientific literature (PMID: 15726418), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1400V missense unknown BRCA1 M1400V does not lie within any known functional domains of the Brca1 protein (UniProt.org). M1400V restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111), but demonstrates only partial restoration of homologous recombination repair activity and some residual binding to Palb2 in vitro (PMID: 19369211) and therefore, its effect on Brca1 protein function is unknown.
K739E missense unknown BRCA1 K739E lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). K739E has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
R71G missense no effect BRCA1 R71G does not lie within any known functional domains of the Brca1 protein (UniProt.org). R71G demonstrates homologous recombination and centrosome duplication similar to wild-type Brca1 in cell culture (PMID: 21725363).
E1282V missense no effect - predicted BRCA1 E1282V does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1282V restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
R1699W missense loss of function - predicted BRCA1 R1699W lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). R1699W results in decreased in decreased Brca1 transcriptional activity in cultured cells (PMID: 11157798) and therefore, is predicted to result in a loss of Brca1 protein function.
M1663L missense no effect BRCA1 M1663L lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1663L demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
K56N missense unknown BRCA1 K56N lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). K56N has not been characterized, but may disrupt hydrogen bonding to S91 of UbcH5b and weaken binding to E2 as determined by structural modeling (PMID: 16403807).
N1236K missense no effect - predicted BRCA1 N1236K does not lie within any known functional domains of the Brca1 protein (UniProt.org). N1236K restores proliferation to a similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
K1110del deletion no effect - predicted BRCA1 K1110del results in the deletion of one amino acid of the Brca1 protein at amino acid 1110 (UniProt.org). K1110del restores proliferation to a similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
V1713fs frameshift loss of function - predicted BRCA1 V1713fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 1713 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). V1713fs has not been characterized, however, other BRCT domain deletion mutants downstream of V1713 are destablizing (PMID: 14534301), thus, V1713fs is predicted to lead to a loss of Brca1 protein function.
V412L missense unknown BRCA1 V412L lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). V412L has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S153R missense unknown BRCA1 S153R does not lie within any known functional domains of the Brca1 protein (UniProt.org). S153R is conflicting, as it repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but demonstrates reduced activity by the single-strand annealing pathway in cell culture (PMID: 23161852).
L631Qfs*4 frameshift loss of function - predicted BRCA1 L631Qfs*4 indicates a shift in the reading frame starting at amino acid 631 and terminating 4 residues downstream causing a premature truncation of the 1863 amino acid Brca1 protein (UniProt.org). L631Qfs*4 has not been characterized, however, C-terminal deletion mutants downstream of L631 are inactivating (PMID: 16618730), thus, L631Qfs*4 is predicted to lead to a loss of Brca1 protein function.
F1734S missense unknown BRCA1 F1734S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). F1734S has not been characterized, but is predicted to result in decreased stability of Brca1 and Tp53 binding by computational modeling (PMID: 17161371).
P1856S missense no effect BRCA1 P1856S does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1856S demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
Y1853* nonsense no effect - predicted BRCA1 Y1853* results in a premature truncation of the Brca1 protein at amino acid 1853 of 1863 (UniProt.org). Y1853* results in colony size similar to wild-type Brca1 in yeast (PMID: 21922593) and therefore, is predicted to have no effect on Brca1 protein function.
V1736G missense loss of function BRCA1 V1736G lies within the BRCT1 domain of the Brca1 protein (UniProt.org). V1736G results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
K893N missense unknown BRCA1 K893N lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). K893N has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
P875S missense unknown BRCA1 P875S lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). P875S has been identified in sequencing studies (PMID: 25759019), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
D1739E missense loss of function BRCA1 D1739E does not lie within any known functional domains of the Brca1 protein (UniProt.org). D1739E results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
E489G missense unknown BRCA1 E489G lies within the Rad50-binding region and the MB1-binding region of the Brca1 protein (PMID: 22737296). E489G has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1009P missense unknown BRCA1 S1009P lies within the Rad51 binding region of the Brca1 protein (PMID: 22737296). S1009P has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
T1685I missense loss of function BRCA1 T1685I lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1685I results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
W1782C missense no effect - predicted BRCA1 W1782C lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). W1782C restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to result in a loss of Brca2 protein function.
S1613G missense no effect - predicted BRCA1 S1613G does not lie within any known functional domains of the Brca1 protein (UniProt.org). S1613G is a common Brca1 polymorphism, and does not impact on Brca1 protein function in cell culture (PMID: 17308087) and therefore, is predicted to have no effect on Brca1 protein function.
R1589H missense no effect - predicted BRCA1 R1589H does not lie within any known functional domains of the Brca1 protein (UniProt.org). R1589H demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 23613828) and therefore, is predicted to have no effect on Brca1 protein function.
I26N missense unknown BRCA1 I26N lies within the RING-type Zinc finger of the Brca1 protein (UniProt.org). I26N has not been characterized, but is predicted to disrupt the interaction with the E2 ubiquitin conjugating enzyme, UbcH5a, by structural modeling (PMID: 16403807).
S663N missense unknown BRCA1 S663N lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). S663N has been identified in the scientific literature (PMID: 17088437), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1689R missense loss of function BRCA1 M1689R lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1689R results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
L82P missense loss of function - predicted BRCA1 L82P does not lie within any known functional domains of the Brca1 protein (UniProt.org). L82P results in a loss of Brca1 binding to Bard1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to result in a loss of Brca1 protein function.
I42V missense unknown BRCA1 I42V lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). I42V is conflicting as it results in defective centrosome duplication in cell culture (PMID: 21725363), but demonstrates homology-directed recombination repair and single-strand anneal repair at levels similar to wild-type Brca1 (PMID: 23161852).
T37R missense loss of function BRCA1 T37R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). T37R confers a loss of function on Brca1 protein as indicated by defective homologous recombination in cell culture (PMID: 21725363, PMID: 23161852).
E29V missense unknown BRCA1 E29V lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). E29V has not been characterized, but is predicted to weaken binding to the E2 ubiquitin conjugative enzyme UbcH5a as determined by structural modeling (PMID: 16403807).
D67Y missense unknown BRCA1 D67Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). D67Y resulted in impaired centrosome duplication in cell culture (PMID: 21725363), however, demonstrated normal function in homologous recombination and binding to Bard1 (PMID: 20103620).
V11A missense no effect - predicted BRCA1 V11A does not lie within any known functional domains of the Brca1 protein (UniProt.org). V11A inhibited satellite transcripts to a level similar to wild-type Brca1 protein in cell culture (PMID: 21901007) and therefore, is predicted to have no effect on Brca1 protein function.
N810Y missense no effect - predicted BRCA1 N810Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). N810Y restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
E33A missense loss of function BRCA1 E33A lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). E33A confers a loss of function to the Brca1 protein as indicated by impaired growth inhibition and nuclear spot formation in yeast (PMID: 21922593).
A1708V missense loss of function BRCA1 A1708V lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). A1708V results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
L392Qfs*5 frameshift loss of function - predicted BRCA1 L392Qfs*5 indicates a shift in the reading frame starting at amino acid 392 and terminating 5 residues downstream causing a premature truncation of the 1863 amino acid Brca1 protein (UniProt.org). L392Qfs*5 has not been characterized, however, C-terminal deletion mutants downstream of L392 are inactivating (PMID: 16618730), thus, L392Qfs*5 is predicted to lead to a loss of Brca1 protein function.
loss unknown loss of function BRCA1 loss indicates loss of the BRCA1 gene, mRNA, and protein.
V525A missense unknown BRCA1 V525A lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). V525A has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
D1778N missense no effect BRCA1 D1778N lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). D1778N results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
E1644G missense no effect - predicted BRCA1 E1644G lies within the BRCT1 domain of the Brca1 protein (UniProt.org). E1644G demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 17308087) and therefore, is predicted to have no effect on Brca1 protein function.
E1114fs frameshift loss of function - predicted BRCA1 E1114fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 1114 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). E1114fs has not been characterized, however, other BRCT domain deletion mutants downstream of E1114 are destabilizing (PMID: 14534301), thus E1114fs is predicted to lead to a loss of Brca1 protein function.
E1735K missense unknown BRCA1 E1735K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). E1735K demonstrates conflicting effects on Brca1 as it impairs functionality in cisplatin sensitivity tests (PMID: 23867111), but maintains homology-directed DNA-repair activity in culture, while losing solubility of the BRCT domain (PMID: 30257991), and therefore, its effect on Brca1 protein function is unknown.
C47F missense loss of function - predicted BRCA1 C47F lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C47F results in failure to suppress colony size in yeast (PMID: 21922593) and therefore, is predicted to confer a loss of function to the Brca1 protein.
N1309H missense unknown BRCA1 N1309H does not lie within any known functional domains of the Brca1 protein (UniProt.org). N1309H has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S377_N417del deletion unknown BRCA1 S377_N417del results in the deletion of 41 amino acids in the Brca1 protein (UniProt.org). S377_N417del has been identified in the scientific literature (PMID: 28588062), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Aug 2018).
E1682V missense no effect BRCA1 E1682V lies within the BRCT1 domain of the Brca1 protein (UniProt.org). E1682V results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
P832S missense unknown BRCA1 P832S lies within the Rad51-binding region of the Brca1 protein (PMID: 22737296). P832S has been identified in sequencing studies (PMID: 17088437), but has not been biochemically characterized and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1841N missense loss of function BRCA1 S1841N lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). S1841N results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
V1833E missense loss of function - predicted BRCA1 V1833E lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1833E results in a loss of Brca1 transcription activity in yeast (PMID: 10811118) and therefore, is predicted to result in a loss of Brca1 protein function.
R170Q missense unknown BRCA1 R170Q does not lie within any known functional domains of the Brca1 protein (UniProt.org). R170Q is conflicting, as it repairs DNA double-strand breaks by homology-directed recombination similar to wild-type Brca1, but with reduced activity by the single-strand annealing pathway in cell culture (PMID: 23161852), and therefore, its effect on Brca1 protein function is unknown.
E453D missense unknown BRCA1 E453D lies within the Rad50-binding region and the MB1-binding region of the Brca1 protein (PMID: 22737296). E453D has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
D96N missense no effect BRCA1 D96N does not lie within any known functional domains of the Brca1 protein (UniProt.org). D96N demonstrates binding to Bard1 and E2 at levels similar to wild-type Brca1 in an in vitro assay (PMID: 16403807).
Y1703S missense loss of function - predicted BRCA1 Y1703S lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). Y1703S results in a loss of Brca1 transcription activity in cell culture (PMID: 23613828) and therefore, is predicted to result in a loss of Brca1 protein function.
I89N missense unknown BRCA1 I89N does not lie within any known functional domains of the Brca1 protein (UniProt.org). I89N has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
S1651P missense loss of function - predicted BRCA1 S1651P lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1651P is predicted to confer a loss of function on Brca1 protein as indicated by failure to restore proliferation in Brca1-null embryonic stem cells in culture (PMID: 23867111).
V1378I missense no effect - predicted BRCA1 V1378I does not lie within any known functional domains of the Brca1 protein (UniProt.org). V1378I restores proliferation to a level similar to wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
C47G missense loss of function BRCA1 C47G lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C47G confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
D1692Y missense loss of function BRCA1 D1692Y lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). D1692Y results in defective Brca1 protein folding and decreased transcription activity in cell culture (PMID: 20516115).
Q12Y missense loss of function - predicted BRCA1 Q12Y does not lie within any known functional domains of the Brca1 protein (UniProt.org). Q12Y results in a loss of Brca1 binding to Bard1 in an in vitro assay (PMID: 16403807) and therefore, is predicted to result in a loss of Brca1 protein function.
N682* nonsense loss of function - predicted BRCA1 N682* results in a premature truncation of the Brca1 protein at amino acid 682 of 1863 (UniProt.org). N682* has not been characterized, however, other C-terminal deletion mutants downstream of N682 are inactivating (PMID: 16618730), thus N682* is predicted to lead to a loss of Brca1 protein function.
G1077W missense unknown BRCA1 G1077W does not lie within any known functional domains of the Brca1 protein (UniProt.org). G1077W has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
M1652K missense loss of function BRCA1 M1652K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). M1652K confers a loss of function on Brca1 protein as indicated by failure to inhibit colony size in yeast (PMID: 15004537) and loss of transcription activity in yeast assays (PMID: 10811118).
I31N missense unknown BRCA1 I31N lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). I31N has not been characterized, but is predicted to disrupt the RING domain of Brca1 as determined by structural modeling (PMID: 16403807).
P1614S missense no effect - predicted BRCA1 P1614S does not lie within any known functional domains of the Brca1 protein (UniProt.org). P1614S demonstrates transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 17308087) and therefore, is predicted to have no effect on Brca1 protein function.
V1809F missense loss of function BRCA1 V1809F lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1809F results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
L358R missense no effect - predicted BRCA1 L358R lies within the RB-binding region and the Rad50-binding region of the Brca1 protein (PMID: 22737296). L358R shows results similar to wild-type in cisplatin sensitivity assays (PMID: 23867111), and therefore, is predicted to have no effect on Brca1 protein function.
V1809A missense loss of function - predicted BRCA1 V1809A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1809A results in moderate decrease of both Brca1 binding to BRCT and transcription activity in cell culture (PMID: 20516115) and therefore, is predicted to result in a loss of Brca1 protein function.
R610M missense unknown BRCA1 R610M lies within the Rad50-binding region of the Brca1 protein (PMID: 22737296). R610M has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
H1805P missense no effect BRCA1 H1805P lies within the BRCT2 domain of the Brca1 protein (UniProt.org). H1805P results in BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
V1833M missense loss of function - predicted BRCA1 V1833M lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). V1833M results in reduced Brca1 transcription activity in cell culture (PMID: 18992264) and therefore, is predicted to result in a loss of Brca1 protein function.
R1699L missense no effect - predicted BRCA1 R1699L lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). R1699L demonstrates transcriptional activity similar to wild-type Brca1 protein in cultured cells (PMID: 24845084) and therefore, is predicted to have no effect on Brca1 protein function.
N1309I missense unknown BRCA1 N1309I does not lie within any known functional domains of the Brca1 protein (UniProt.org). N1309I has not been characterized in the scientific literature and therefore, its effect on Brca1 protein function is unknown (PubMed, Nov 2018).
E29Sfs*2 frameshift loss of function - predicted BRCA1 E29Sfs*2 indicates a shift in the reading frame starting at amino acid 29 and terminating 2 residues downstream causing a premature truncation of the 1863 aa Brca1 protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), E29Sfs*2 is predicted to result in a loss of Brca1 protein function; however, the corresponding cDNA change has been demonstrated to act as a reversion mutation in the context of a specific inactivating BRCA1 mutation, leading to restoration of the BRCA1 open reading frame and wild-type protein function, as demonstrated by induction of Brca1 foci formation following ionizing irradiation in vitro and association with acquired resistance to platinum-based chemotherapy (PMID: 28765325). Y
I1766S missense loss of function BRCA1 I1766S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). I1766S results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
M1783I missense no effect BRCA1 M1783I lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1783I demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115).
H41R missense loss of function BRCA1 H41R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). H41R confers a loss of function on Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
P1806A missense no effect BRCA1 P1806A lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). P1806A demonstrates BRCT binding and transcription activity similar to wild-type Brca1 protein in cell culture (PMID: 20516115, PMID: 17308087).
T1691K missense loss of function BRCA1 T1691K lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). T1691K results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
C24R missense loss of function BRCA1 C24R lies within the RING-type zinc finger region of the Brca1 protein (UniProt.org). C24R confers a loss of function to the Brca1 protein as indicated by defective homologous recombination and centrosome duplication in cell culture (PMID: 21725363).
I1807S missense loss of function - predicted BRCA1 I1807S lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). I1807S results in a loss of Brca1 transcription activity in yeast (PMID: 12496477) and therefore, is predicted to result in a loss of Brca1 protein function.
M1783T missense loss of function BRCA1 M1783T lies within the BRCT domain 2 of the Brca1 protein (UniProt.org). M1783T results in moderate defects in BRCT binding and Brca1 transcription activity in cell culture (PMID: 20516115) and demonstrates reduced homology-directed repair activity compared to wild-type Brca1 in vitro (PMID: 26689913).
E1346K missense no effect - predicted BRCA1 E1346K does not lie within any known functional domains of the Brca1 protein (UniProt.org). E1346K restores proliferation to similar level of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
S1722F missense loss of function BRCA1 S1722F lies within the BRCT domain 1 of the Brca1 protein (UniProt.org). S1722F results in defective Brca1 protein folding and BRCT binding, and decreased transcription activity in cell culture (PMID: 20516115).
Q1756fs frameshift loss of function - predicted BRCA1 Q1756fs results in a change in the amino acid sequence of the Brca1 protein beginning at aa 1756 of 1863, likely resulting in premature truncation of the functional protein (UniProt.org). Q1756fs has not been characterized, however, other BRCT domain deletion mutants downstream of Q1756 are destablizing (PMID: 14534301), thus Q1756fs is predicted to lead to a loss of Brca1 protein function.
V1741G missense loss of function BRCA1 V1741G does not lie within any known functional domains of the Brca1 protein (UniProt.org). V1741G results in defective Brca1 binding to BRCT and decreased transcription activity in cell culture (PMID: 20516115).
L246V missense no effect - predicted BRCA1 L246V does not lie within any known functional domains of the Brca1 protein (UniProt.org). L246V restores proliferation to a level similar to that of wild-type Brca1 in Brca1-null embryonic stem cells in culture (PMID: 23867111) and therefore, is predicted to have no effect on Brca1 protein function.
I68K missense unknown BRCA1 I68K does not lie within any known functional domains of the Brca1 protein (UniProt.org). I68K has not been characterized, but is predicted to disrupt the RING domain of Brca1 as determined by structural modeling (PMID: 16403807).
Molecular Profile Protein Effect Treatment Approaches
BRCA1 M1008I no effect - predicted
BRCA1 L269V unknown
BRCA1 A1830T no effect
BRCA1 K991Q unknown
BRCA1 L30F no effect - predicted
BRCA1 I90T no effect - predicted
BRCA1 I31M loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R866C no effect - predicted
BRCA1 L1407P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1258D unknown
BRCA1 E515V unknown
BRCA1 F1695L no effect - predicted
BRCA1 V191I no effect - predicted
BRCA1 V1838E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1775K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1733G no effect
BRCA1 M1663K no effect
BRCA1 G1763V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Y1853C loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E23Vfs*17 BRCA1 E29Sfs*2 BRCA1 K38Sfs*12
BRCA1 K38Sfs*12 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1566G unknown
BRCA1 K996Q unknown
BRCA1 S1512I no effect - predicted
BRCA1 A1752V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K1207N unknown
BRCA1 L1854P unknown
BRCA1 P1856T loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V627I unknown
BRCA1 A1789S no effect
BRCA1 L1795Pfs*3 loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K1183R unknown
BRCA1 D1123Y unknown
BRCA1 C27A loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K1109T unknown
BRCA1 R1753T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1736A loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1448G no effect - predicted
BRCA1 I1318Lfs*7 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T1720I no effect - predicted
BRCA1 M1652T no effect
BRCA1 G1788D loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 H513Y unknown
BRCA1 F1761S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1775R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1628T no effect
BRCA1 L28P unknown
BRCA1 L63F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1778Y no effect
BRCA1 E577* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K45T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P798L no effect - predicted
BRCA1 Y105C unknown
BRCA1 D1739V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 N1730S no effect
BRCA1 I31T unknown
BRCA1 V1665M no effect - predicted
BRCA1 G57R unknown
BRCA1 C39S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Y179C loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C24Y unknown
BRCA1 R1443* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C1697R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 G1384W unknown
BRCA1 G1743R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S4F unknown
BRCA1 P1812R no effect - predicted
BRCA1 V1653M loss of function
BRCA1 S308A unknown
BRCA1 E907K unknown
BRCA1 V1808A no effect
BRCA1 R1835P unknown
BRCA1 P871L unknown
BRCA1 V1714G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1655fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C44Y unknown
BRCA1 R1726G no effect
BRCA1 S1613C unknown
BRCA1 A1843P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Q1409L no effect - predicted
BRCA1 P1771L loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1810G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 W1718L loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 G1706E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D435Y unknown
BRCA1 M1411T unknown
BRCA1 M18K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R1751P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 F461C unknown
BRCA1 S1101N no effect
BRCA1 E851G unknown
BRCA1 N1647K no effect
BRCA1 Q202* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 H619N unknown
BRCA1 V191D unknown
BRCA1 C39R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1682K no effect
BRCA1 T1852S unknown
BRCA1 K1254T unknown
BRCA1 K45N loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P1812S unknown
BRCA1 V899L unknown
BRCA1 F1704S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 H1862L no effect - predicted
BRCA1 M1783L no effect
BRCA1 A942V unknown
BRCA1 K38N no effect - predicted
BRCA1 N550H no effect - predicted
BRCA1 Q1811R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 H1402Y no effect - predicted
BRCA1 Q356R loss of function
BRCA1 E1794D no effect
BRCA1 W1718C loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P1776S unknown
BRCA1 S1715N loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C47W unknown
BRCA1 M1? loss of function - predicted
BRCA1 D1818G no effect
BRCA1 H1746N loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 G275D unknown
BRCA1 E1419K unknown
BRCA1 D821Y unknown
BRCA1 mut ERBB2 neg
BRCA1 mut TP53 E298*
BRCA1 mutant unknown
BRCA1 mut TP53 Y220C
BRCA1 A622V unknown
BRCA1 R1751Q no effect
BRCA1 V1590A unknown
BRCA1 G1803A loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1651F no effect
BRCA1 S1715C loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1344H unknown
BRCA1 V1714A unknown
BRCA1 S1164G unknown
BRCA1 L1657P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E515G unknown
BRCA1 G1706A no effect
BRCA1 G1738R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E515Q unknown
BRCA1 T1685A loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1778H unknown
BRCA1 A1752P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K1702E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1628V no effect - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 G1738E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 F1761I loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M18T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I21V unknown PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T231M no effect - predicted
BRCA1 Q1785H no effect
BRCA1 L1844R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 W1782* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1836K unknown
BRCA1 P1812A no effect - predicted
BRCA1 M1775V no effect - predicted
BRCA1 W321C unknown
BRCA1 E143K unknown
BRCA1 Q1756* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Q1299L unknown
BRCA1 E1214K no effect - predicted
BRCA1 G1656D no effect - predicted
BRCA1 D1692H loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C644W unknown
BRCA1 L1664P no effect
BRCA1 S1294G unknown
BRCA1 W1718S loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P1859R no effect
BRCA1 L52F unknown PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R1589P no effect - predicted
BRCA1 S1596Nfs*25 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 A1823T no effect
BRCA1 E1060A no effect - predicted
BRCA1 L1564P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Q94* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 W1837G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K339fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E23fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1512A unknown
BRCA1 dec exp no effect
BRCA1 dec exp MET dec exp
BRCA1 dec exp MET over exp
BRCA1 P1749R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 W1837C loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 del loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T1700A loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1739G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T1393A unknown
BRCA1 L49M no effect - predicted
BRCA1 negative loss of function
BRCA1 L165P no effect - predicted
BRCA1 C1787S no effect
BRCA1 L1705P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I124V unknown
BRCA1 C64G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I89T no effect - predicted
BRCA1 P142H unknown
BRCA1 L1267S no effect - predicted
BRCA1 A1843T loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1692N unknown
BRCA1 S186Y no effect - predicted
BRCA1 E427_S713del unknown
BRCA1 R170W no effect - predicted
BRCA1 Q1826H no effect - predicted
BRCA1 L1570P unknown
BRCA1 S988A unknown
BRCA1 C44F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 A1789T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1027I unknown
BRCA1 A314T unknown
BRCA1 E1258G unknown
BRCA1 N1309Ifs*9 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R1589C unknown
BRCA1 S4P no effect - predicted
BRCA1 L147F no effect - predicted
BRCA1 S1297del no effect - predicted
BRCA1 K654fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L1764P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L1780P loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 F1662S no effect
BRCA1 N1819Y no effect - predicted
BRCA1 M1652I no effect
BRCA1 Y856H no effect - predicted
BRCA1 G1770V loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D695N no effect - predicted
BRCA1 R1443G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1040N unknown
BRCA1 S1211F unknown
BRCA1 S561Y unknown
BRCA1 R841Q no effect - predicted
BRCA1 W1837R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1503* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L574I unknown
BRCA1 H1686Q loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D245V no effect - predicted
BRCA1 inact mut loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 inact mut TP53 inact mut
BRCA1 S59R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1534M no effect - predicted
BRCA1 R841W no effect - predicted
BRCA1 R1203* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R133H unknown
BRCA1 R320T unknown
BRCA1 T1720A no effect
BRCA1 E962A unknown
BRCA1 L668F no effect
BRCA1 R1347G no effect - predicted
BRCA1 T37Qfs*13 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E23Vfs*17 BRCA1 T37Qfs*13
BRCA1 P1637L no effect - predicted
BRCA1 K45Q no effect
BRCA1 D1739Y loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I15T unknown
BRCA1 D1344N unknown
BRCA1 M1775E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C360R unknown
BRCA1 S1655F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T1691I loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T826K loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C1767S no effect - predicted
BRCA1 A1669S no effect
BRCA1 V1696L loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1841A loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V271L no effect - predicted
BRCA1 V340* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C39Y loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K1487R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E23Vfs*17 loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1586G no effect - predicted
BRCA1 Q155E unknown
BRCA1 F79S unknown
BRCA1 S1473P no effect - predicted
BRCA1 V1804D unknown
BRCA1 E1038G no effect - predicted
BRCA1 Y1703H loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1778G no effect
BRCA1 V1804A no effect - predicted
BRCA1 A1708E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E404D unknown
BRCA1 E673* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 H1421Y no effect - predicted
BRCA1 S1841R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 N1819S no effect
BRCA1 G1788V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1000Q unknown
BRCA1 E1660G loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 A1752G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E362H no effect - predicted
BRCA1 H1686R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S1164I loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P1771R loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D853N unknown
BRCA1 S1715R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C61G unknown PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C61G TP53 loss
BRCA1 K50E unknown
BRCA1 D1546N no effect - predicted
BRCA1 T77M loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K65M unknown
BRCA1 F1734L loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R1699Q loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K50L unknown
BRCA1 D693N no effect - predicted
BRCA1 E1250K no effect - predicted
BRCA1 Q1756C unknown
BRCA1 S72R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1688del loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1851E no effect
BRCA1 S1486C no effect - predicted
BRCA1 wild-type no effect
BRCA1 wild-type BRCA2 wild-type
BRCA1 M1689T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 S784L unknown
BRCA1 M1400V unknown
BRCA1 K739E unknown
BRCA1 R71G no effect
BRCA1 E1282V no effect - predicted
BRCA1 R1699W loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1663L no effect
BRCA1 K56N unknown
BRCA1 N1236K no effect - predicted
BRCA1 K1110del no effect - predicted
BRCA1 V1713fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V412L unknown
BRCA1 S153R unknown
BRCA1 L631Qfs*4 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 F1734S unknown
BRCA1 P1856S no effect
BRCA1 Y1853* no effect - predicted
BRCA1 V1736G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 K893N unknown
BRCA1 P875S unknown
BRCA1 D1739E loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E489G unknown
BRCA1 S1009P unknown
BRCA1 T1685I loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 W1782C no effect - predicted
BRCA1 S1613G no effect - predicted
BRCA1 R1589H no effect - predicted
BRCA1 I26N unknown
BRCA1 S663N unknown
BRCA1 M1689R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L82P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I42V unknown PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 T37R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E29V unknown
BRCA1 D67Y unknown PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V11A no effect - predicted
BRCA1 N810Y no effect - predicted
BRCA1 E33A loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 A1708V loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L392Qfs*5 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 loss loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 loss FGFR2-DNM3
BRCA1 loss TP53 loss
BRCA1 V525A unknown
BRCA1 D1778N no effect
BRCA1 E1644G no effect - predicted
BRCA1 E1114fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1735K unknown
BRCA1 C47F loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 N1309H unknown
BRCA1 S377_N417del unknown
BRCA1 E1682V no effect
BRCA1 P832S unknown
BRCA1 S1841N loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1833E loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R170Q unknown
BRCA1 E453D unknown
BRCA1 D96N no effect
BRCA1 Y1703S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I89N unknown
BRCA1 S1651P loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1378I no effect - predicted
BRCA1 C47G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 D1692Y loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Q12Y loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 N682* loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 G1077W unknown
BRCA1 M1652K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I31N unknown
BRCA1 P1614S no effect - predicted
BRCA1 V1809F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L358R no effect - predicted
BRCA1 V1809A loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R610M unknown
BRCA1 H1805P no effect
BRCA1 V1833M loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 R1699L no effect - predicted
BRCA1 N1309I unknown
BRCA1 E29Sfs*2 loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I1766S loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1783I no effect
BRCA1 H41R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 P1806A no effect
BRCA1 T1691K loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 C24R loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 I1807S loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 M1783T loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 E1346K no effect - predicted
BRCA1 S1722F loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 Q1756fs loss of function - predicted PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 V1741G loss of function PARP Inhibitor (Pan) PARP-1 Inhibitor
BRCA1 L246V no effect - predicted
BRCA1 I68K unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRCA1 E23Vfs*17 BRCA1 E29Sfs*2 BRCA1 K38Sfs*12 ovarian cancer predicted - resistant Carboplatin Clinical Study Actionable In a clinical study, an ovarian cancer patient harboring BRCA1 E23Vfs*17 progressed while being treated with platinum-based chemotherapy, and via cell-free DNA testing was found to have acquired somatic reversion mutations, BRCA1 E29Sfs*2 and BRCA1 K38Sfs*12, which restored the open reading frame, resulting in wild-type BRCA1 protein function (PMID: 28765325). 28765325
BRCA1 L1795Pfs*3 breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) inhibited growth of human breast cancer cells harboring BRCA1 L1795Pfs*3 (referred to as BRCA1 5382insC) in culture, and resulted in prolonged overall survival in transgenic mouse models of breast cancer (PMID: 27454287). 27454287
BRCA1 mut TP53 E298* ovarian cancer predicted - sensitive MK-1775 + Carboplatin Phase II Actionable In a Phase II trial, Paraplatin (carboplatin) and MK-1775 combination treatment resulted in partial response in an ovarian cancer patient harboring TP53 E298* and mutations in BRCA1 (PMID: 27998224). 27998224
BRCA1 mutant triple-receptor negative breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) inhibited the growth of triple-receptor negative BRCA1-mutant breast cancer cell lines under hypoxic conditions (PMID: 25193512). 25193512
BRCA1 mutant breast cancer not applicable Denosumab Clinical Study Emerging In a clinical study, Xgeva (denosumab) inhibited cell proliferation in normal breast tissues of BRCA1 mutation carriers, provided a potential strategy to prevent breast cancer in this population (PMID: 27322743). 27322743
BRCA1 mutant Her2-receptor negative breast cancer sensitive Olaparib FDA approved Actionable In a Phase III trial (OlympiAD) that supported FDA approval, Lynparza (olaparib) treatment resulted in significantly improved median progression-free survival (7.0 vs 4.2 months, HR=0.58, p<0.001) and higher response rate (59.9% vs 28.8%) compared to standard chemotherapy in ERBB2 (HER2)-negative breast cancer patients harboring a germline BRCA mutation (PMID: 28578601; NCT02000622). 28578601
BRCA1 mutant breast cancer sensitive Olaparib Phase II Actionable In a Phase II trial, Lynparza (olaparib) demonstrated safety and efficacy in breast cancer patients with BRCA1 mutations, with an objective response rate of 50% (9/18) in the maximum tolerated dose cohort and 19% (3/16) in the lower dose cohort (PMID: 20609467). 20609467
BRCA1 mutant triple-receptor negative breast cancer decreased response Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in patients with triple-receptor negative breast cancer carrying a BRCA1 and/or BRCA2 mutation resulted in a lower clinical benefit rate (56% vs 89%) compared to treatment in non-triple-receptor negative breast cancer patients carrying a BRCA1/2 mutation (PMID: 28242752). 28242752
BRCA1 mutant ovarian carcinoma no benefit Bevacizumab + Carboplatin + Paclitaxel Clinical Study Actionable In a clinical study, ovarian carcinoma patients harboring a mutation in either BRCA1, BRCA2, or another homologous recombination repair (HRR) gene did not demonstrate a significant difference in progression free survival when Avastin (bevacizumab) was added to the combined platinum therapy, Platinol (carboplatin) and Taxol (paclitaxel), versus the platinum therapy with placebo, suggesting HRR gene mutations do not impact the effect of Avastin (bevacizumab) (PMID: 29191972). 29191972
BRCA1 mutant breast cancer sensitive AZD2461 Preclinical - Cell culture Actionable In a preclinical study, AZD2461 inhibited the growth of BRCA1 mutant breast cancer cells in culture (PMID: 27550455). 27550455
BRCA1 mutant breast cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in breast cancer patients harboring germline deleterious BRCA1/2 mutations resulted in an objective response rate of 50% (7/14) including one patient with a complete response and six patients with a partial response and a median progression free survival of 34.6 weeks (PMID: 28242752). 28242752
BRCA1 mutant breast cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I clinical trial, Talazoparib (BMN-673) was well-tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring deleterious BRCA1/2 mutations, including objective responses in 33% (2/6) of breast cancer patients carrying BRCA mutations (J Clin Oncol 31, 2013 (suppl; abstr 2580)). detail...
BRCA1 mutant breast cancer sensitive Pamiparib Preclinical - Cell line xenograft Actionable In a preclinical study, BGB-290 inhibited PARylation and demonstrated anti-tumor activity in cell line xenograft models of breast cancer harboring BRCA1 mutations (Cancer Res 2015; 75(15 Suppl): Abstract nr 1653). detail...
BRCA1 mutant ovarian cancer predicted - sensitive Pamiparib Phase I Actionable In a Phase I trial, BGB-290 treatment resulted in improved objective response rate in ovarian cancer patients harboring germline BRCA1/2 mutations (58%, 7/12) compared to BRCA1/2 wild-type (25%, 2/8) patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 368PD; NCT02361723). detail...
BRCA1 mutant breast cancer predicted - sensitive Niraparib Phase I Actionable In a Phase I clinical trial, Zejula (niraparib) was well-tolerated and demonstrated preliminary efficacy in advanced solid tumor patients, including partial responses in 50% (2/4) of breast cancer patients carrying BRCA1 or BRCA2 mutations (PMID: 23810788). 23810788
BRCA1 mutant pancreatic cancer predicted - sensitive Rucaparib Phase II Actionable In a Phase II trial, Rubraca (rucaparib) treatment resulted in an objective response rate of 11% (2/19) and a disease control rate of 32% (6/19) in advanced pancreatic cancer patients with a known deleterious BRCA mutation, of whom 79% harbored a BRCA2 mutation (J Clin Oncol 34, 2016 (suppl; abstr 4110)). detail...
BRCA1 mutant ovarian cancer predicted - sensitive Niraparib Phase III Actionable In a Phase III trial (NOVA), maintenance Zejula (niraparib) therapy significantly improved median progression-free survival compared to placebo (21.0 vs. 5.5 months, HR=0.27) in patients with platinum-sensitive, recurrent ovarian cancer harboring germline BRCA mutations (PMID: 27717299; NCT01847274). 27717299
BRCA1 mutant breast cancer predicted - sensitive Veliparib + Carboplatin Phase I Actionable In a Phase I clinical trial, the combination of Veliparib (ABT-888) and Paraplatin (carboplatin) demonstrated preliminary efficacy in metastatic breast cancer patients, with partial response in 25% (4/16) and stable disease in 62.5% (10/16) of patients with BRCA1/2 mutations or Fanconi Anemia pathway defects (J Clin Oncol 32:5s, 2014 (suppl; abstr 1074)). detail...
BRCA1 mutant ovarian cancer sensitive Olaparib FDA approved Actionable In a Phase II trial that supported FDA approval, treatment with Lynparza (olaparib) resulted in a tumor response rate of 34% (n=137) and median duration of response of 7.9 months in ovarian cancer patients harboring germline BRCA1/2 mutations that had received 3 or more lines of chemotherapy (PMID: 26187614, PMID: 25366685; NCT01078662). 26187614 25366685
BRCA1 mutant ovarian cancer sensitive Olaparib Guideline Actionable Lynparza (olaparib) is included in the guidelines as recurrence therapy for ovarian cancer patients harboring BRCA1/2 germline mutations (NCCN.org). detail...
BRCA1 mutant ovarian cancer sensitive Olaparib Phase III Actionable In a Phase III trial, ovarian cancer patients who are platinum-sensitive and relapsed and harbor either mutant BRCA1 or mutant BRCA2 demonstrated a greater progression-free survival (19.1 mo vs 5.5 mo) when treated with Lynparza (olaparib) tablets as maintenance therapy compared to placebo (PMID: 28754483; NCT01874353). 28754483
BRCA1 mutant ovarian cancer predicted - sensitive Irinotecan + Veliparib Phase I Actionable In a Phase I trial, Veliparib (ABT-888) and Camptosar (irinotecan) combination therapy resulted in partial response in 11% (1/9) and stable disease in 67% (6/9) of ovarian cancer patients harboring germline mutations in BRCA1 or BRCA2 (PMID: 26842236). 26842236
BRCA1 mutant ovarian cancer sensitive Rucaparib Phase III Actionable In a Phase III trial (ARIEL3), Rubraca (rucaparib) treatment resulted in significantly improved progression-free survival compared to placebo (16.6 vs 5.4 months, HR=0.23, p=0.0001) in patients with BRCA-mutant, platinum-sensitive ovarian cancer (PMID: 28916367; NCT01968213). 28916367
BRCA1 mutant ovarian cancer sensitive Rucaparib FDA approved Actionable In a retrospective analysis of two Phase II trials (ARIEL2 and Study 10) that supported FDA approval, Rubraca (rucaparib) treatment resulted in an objective response rate of 54% (36/67) in high-grade ovarian cancer patients harboring BRCA1 mutations (PMID: 28751443). 28751443
BRCA1 mutant ovarian cancer sensitive Rucaparib Guideline Actionable Rubraca (rucaparib) is included in the guidelines as recurrence therapy for ovarian cancer patients harboring BRCA1/2 germline mutations (NCCN.org). detail...
BRCA1 mutant ovarian cancer sensitive Rucaparib Phase II Actionable In a Phase II clinical trial, treatment with Rubraca (rucaparib) was tolerated and demonstrated activity in ovarian cancer patients with germline BRCA1/2 mutations (PMID: 27002934). 27002934
BRCA1 mutant pancreatic cancer not applicable N/A Guideline Risk Factor Germline BRCA1/2 mutations are associated with increased risk of developing and early onset of pancreatic cancer (NCCN.org). detail...
BRCA1 mutant Advanced Solid Tumor predicted - sensitive CX-5461 Phase I Actionable In a Phase I trial, CX-5461 treatment resulted in partial response in a patient with advanced solid tumor harboring BRCA2 mutations, and stable disease in 5 additional patients, 4 of whom harboring BRCA1/2 mutations, and 1 with Li-Fraumeni syndrome (Annals of Oncology, Volume 29, Issue suppl_3, 1 March 2018, abstract 440; NCT02719977). detail...
BRCA1 mutant ovarian cancer predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN-673) treatment in ovarian cancer patients harboring germline deleterious BRCA1/2 mutations resulted in an objective response rate of 48%, including one complete response, and a clinical benefit rate of 76% at 24 weeks (PMID: 28242752). 28242752
BRCA1 mutant triple-receptor negative breast cancer sensitive Veliparib + Carboplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Veliparib (ABT-888) and Paraplatin (carboplatin) induced DNA damage and decreased tumor growth in an intracranial human BRCA-mutant triple-negative breast cancer cell line xenograft model, but did not provide a significant survival benefit over Paraplatin (carboplatin) alone (PMID: 25824335). 25824335
BRCA1 mutant Advanced Solid Tumor predicted - sensitive ABT-767 Phase I Actionable In a Phase I trial, ABT-767 treatment resulted in a response rate of 18% (n=14/79) in patients with high grade serous ovarian cancer, fallopian tube, or primary peritoneal cancer or with solid tumors harboring germline BRCA1 or BRCA2 mutations, with an overall 6 month time to progression rate of 22% (Ann Oncol (2014) 25 (suppl 4): iv150). detail...
BRCA1 mutant Her2-receptor negative breast cancer sensitive Cisplatin + Veliparib + Vinorelbine Phase I Actionable In a Phase I trial, Veliparib (ABT-888), in combination with Platinol (cisplatin) and Navelbine (vinorelbine), resulted in a greater complete response (7%, 1/14), partial response (50%, 7/14), and 6-month progression free survival rate (71%, 10/14) in Erbb2 (Her2) negative breast cancer patients harboring germline BRCA1 or BRCA2 mutations compared to BRCA wild-type patients (PMID: 26801247). 26801247
BRCA1 mutant breast cancer sensitive NMS-P118 Preclinical - Cell line xenograft Actionable In a preclinical study, NMS-P118 treatment resulted in antitumor activity in BRCA1 mutant breast cancer xenograft models, demonstrating tumor growth inhibition and induction of a complete response (PMID: 26222319). 26222319
BRCA1 mut TP53 Y220C ovarian cancer sensitive Carboplatin + VX-970 Phase I Actionable In a Phase I trial, VX-970 and Paraplatin (carboplatin) combination treatment resulted in partial response for 6 months in a PARP inhibitor-resistant ovarian cancer patient harboring a germline BRCA1 mutation and TP53 Y220C (J Clin Oncol 34, 2016 (suppl; abstr 2504)). detail...
BRCA1 W1782* ovarian carcinoma sensitive Rucaparib Clinical Study Actionable In a clinical study, an ovarian carcinoma patient harboring a BRCA1 W1782* germline mutation demonstrated stable disease when treated with Rubraca (rucaparib) (PMID: 28588062). 28588062
BRCA1 dec exp triple-receptor negative breast cancer sensitive Chlorambucil Preclinical Actionable In a preclinical study, BRCA1 knockdown enhanced growth inhibition by Ambochlorin (chlorambucil) in triple-receptor negative breast cancer cell lines in culture (PMID: 25193512). 25193512
BRCA1 dec exp triple-receptor negative breast cancer sensitive Cisplatin Preclinical Actionable In a preclinical study, knockdown of BRCA1 increased sensitivity of triple-negative breast cancer cells to Platinol (cisplatin) under hypoxic conditions (PMID: 25193512). 25193512
BRCA1 dec exp MET dec exp triple-receptor negative breast cancer sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca1 expression via shRNA knockdown sensitized triple-receptor negative breast cancer cells with low expression of Met to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRCA1 dec exp MET over exp triple-receptor negative breast cancer no benefit Rucaparib Preclinical - Cell culture Actionable In a preclinical study, decreasing Brca1 expression via shRNA knockdown did not sensitize triple-receptor negative breast cancer cells with Met over expression to Rubraca (rucaparib) in culture (PMID: 26779812). 26779812
BRCA1 negative Advanced Solid Tumor sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, BRCA1-deficient cancer cell lines with DNA repair deficiency demonstrated high sensitivity to the PARP inhibitor, Talazoparib (BMN-673) (PMID: 23881923). 23881923
BRCA1 inact mut Advanced Solid Tumor predicted - sensitive Talazoparib Phase I Actionable In a Phase I trial, Talazoparib (BMN673) treatment demonstrated safety and preliminary efficacy in patients with advanced solid tumors harboring deleterious BRCA1/2 mutations (J Clin Oncol 31, 2013 (suppl; abstr 2580)). detail...
BRCA1 inact mut triple-receptor negative breast cancer predicted - sensitive E7449 Preclinical - Cell line xenograft Actionable In a preclinical study, E7449 inhibited tumor growth in a triple-negative breast cancer cell line xenograft model harboring a BRCA1 splice donor site mutation (PMID: 26513298). 26513298
BRCA1 inact mut Advanced Solid Tumor sensitive E7449 Preclinical Actionable In a preclinical study, E7449 inhibited proliferation of a BRCA1-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair pathway mutations (PMID: 26513298). 26513298
BRCA1 inact mut breast cancer sensitive APTO-253 Preclinical - Cell culture Actionable In a preclinical study, APTO-253 treatment resulted in decreased viability of breast cancer cells expressing a BRCA1 inactivating mutation in culture (PMID: 29626126). 29626126
BRCA1 inact mut ovarian cancer no benefit Veliparib + Cyclophosphamide Phase II Actionable In a Phase II clinical trial, the combination of Veliparib (ABT-888) and Cytoxan (cyclophosphamide) did not demonstrate improved response rate or progression-free survival over Cytoxan (cyclophosphamide) alone in ovarian cancer patients harboring deleterious mutations in BRCA1 or BRCA2 (PMID: 25589624). 25589624
BRCA1 inact mut breast cancer predicted - sensitive Carboplatin + Paclitaxel + Veliparib Phase II Actionable In a Phase II trial, the combination of Veliparib (ABT-888), Paraplatin (carboplatin), and Taxol (paclitaxel) resulted in a higher objective response rate (77.8% vs 61.3%) compared to placebo plus Paraplatin (carboplatin) and Taxol (paclitaxel) in breast cancer patients harboring either BRCA1 or BRCA2 deleterious mutations (SABCS, 2016, Abstract # S2-05). detail...
BRCA1 inact mut Her2-receptor negative breast cancer sensitive Talazoparib FDA approved Actionable In a Phase III trial (EMBRACA) that supported FDA approval, Talzenna (talazoparib) treatment resulted in significantly longer median progression-free survival (8.6 vs 5.6 months, HR=0.54, p<0.001), and higher objective response rate (62.6% vs 27.2%, OR=5.0, p<0.001) compared to standard chemotherapy in patients with advanced ERBB2 (HER2)-negative breast cancer harboring known deleterious or suspected deleterious germline mutations in BRCA1 or BRCA2 (PMID: 30110579; NCT01945775). 30110579
BRCA1 inact mut ovarian cancer sensitive Niraparib Phase I Actionable In a Phase I clinical trial, Zejula (niraparib) demonstrated safety and efficacy in ovarian cancer patients with BRCA1 inactivating mutations (PMID: 23810788). 23810788
BRCA1 E23Vfs*17 BRCA1 T37Qfs*13 ovarian cancer predicted - resistant Carboplatin Clinical Study Actionable In a clinical study, an ovarian cancer patient harboring BRCA1 E23Vfs*17 progressed while being treated with platinum-based chemotherapy, and via cell-free DNA testing was found to have acquired a somatic reversion mutation, BRCA1 T37Qfs*13, which restored the open reading frame, resulting in wild-type BRCA1 protein function (PMID: 28765325). 28765325
BRCA1 E23Vfs*17 invasive ductal carcinoma resistant Rucaparib Preclinical - Cell line xenograft Actionable In a preclinical study, breast invasive ductal carcinoma cells harboring BRCA1 E23Vfs*17 (also referred to as BRCA1 185delAG) acquired resistance to Rubraca (rucaparib) both in culture and in cell line xenograft models through the expression of a RING-less Brca1 protein utilizing an in-frame translation start site downstream of the mutation (PMID: 27454289). 27454289
BRCA1 E23Vfs*17 breast cancer decreased response Olaparib Preclinical - Pdx & cell culture Actionable In a preclinical study, breast cancer cells harboring BRCA1 E23Vfs*17 (referred to as BRCA1 185delAG) demonstrated reduced sensitivity, developed resistance to Lynparza (olaparib) in culture and in patient-derived xenograft models due to the expression of a RING-less form of Brca1 (PMID: 27454287). 27454287
BRCA1 E23Vfs*17 invasive ductal carcinoma resistant Cisplatin Preclinical - Cell line xenograft Actionable In a preclinical study, breast invasive ductal carcinoma cells harboring BRCA1 E23Vfs*17 (also referred to as BRCA1 185delAG) acquired resistance to Platinol (cisplatin) both in culture and in cell line xenograft models through the expression of a RING-less Brca1 protein utilizing an in-frame translation start site downstream of the mutation (PMID: 27454289). 27454289
BRCA1 C61G TP53 loss breast cancer decreased response Olaparib Preclinical Actionable In a preclinical study, mouse breast cancer models harboring BRCA1 C61G with conditional loss of Tp53 had a decreased response to Lynparza (olaparib) compared to models with conditional loss of Brca1 and Tp53 (PMID: 22172724). 22172724
BRCA1 wild-type triple-receptor negative breast cancer no benefit Veliparib + Carboplatin Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Veliparib (ABT-888) and Paraplatin (carboplatin) provided no survival benefit in an intracranial human BRCA wild-type triple-negative breast cancer cell line xenograft model (PMID: 25824335). 25824335
BRCA1 wild-type breast cancer resistant Olaparib Preclinical Actionable In a preclinical study, BRCA1 proficient transgenic mouse models of breast cancer did not respond to Lynparza (olaparib) treatment (PMID: 27454287). 27454287
BRCA1 wild-type ovarian cancer sensitive Talazoparib + Temozolomide Phase I Actionable In a Phase I trial, the combination of Talazoparib (BMN-673) and Temodar (temozolomide) resulted in a partial response in 50% (2/4) of ovarian cancer patients harboring wild-type BRCA1 (European Journal of Cancer, Sep 2015, 51:3, S60). detail...
BRCA1 wild-type triple-receptor negative breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) inhibited the growth of triple-receptor negative breast cancer cell lines expressing wild-type BRCA1 under hypoxic conditions (PMID: 25193512). 25193512
BRCA1 wild-type BRCA2 wild-type ovarian cancer predicted - sensitive Niraparib Phase III Actionable In a Phase III trial (NOVA), Zejula (niraparib) maintenance therapy improved median progression-free survival compared to placebo (9.3 vs. 3.9 months, HR=0.45) in platinum-sensitive, recurrent ovarian cancer patients without germline BRCA mutations, with and without homologous recombination deficiency (12.9 vs. 3.8 months, HR=0.38) (PMID: 27717299; NCT01847274). 27717299
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Everolimus + Talazoparib Preclinical - Cell line xenograft Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Talazoparib (BMN-673) when treatment was combined with Afinitor (everolimus), resulting in greater decreased cell proliferation and apoptosis in culture and reduced tumor volume in xenograft models (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Olaparib + KU-0063794 Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Lynparza (olaparib) when treatment was combined with KU-0063794, resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive Olaparib + Everolimus Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Lynparza (olaparib) when treatment was combined with Afinitor (everolimus), resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer sensitive KU-0063794 + Talazoparib Preclinical Actionable In a preclinical study, triple-receptor negative breast cancer cells wild-type for BRCA1/2 demonstrated an increased sensitivity to Talazoparib (BMN673) when treatment was combined with KU-0063794, resulting in greater decreased cell proliferation and apoptosis in culture (PMID: 26546619). 26546619
BRCA1 wild-type BRCA2 wild-type triple-receptor negative breast cancer predicted - sensitive Cisplatin + VX-970 Phase I Actionable In a Phase I trial, VX-970 in combination with Platinol (cisplatin) resulted in an objective response rate of 38.9% (7/18, all partial responses) and a disease control rate of 72.2% (13/18) in patients with BRCA1/2 wild-type triple-receptor negative breast cancer (Ann Oncol 2017, Vol 28, Suppl 5, Abstract # 242PD; NCT02157792). detail...
BRCA1 wild-type BRCA2 wild-type ovarian serous carcinoma predicted - sensitive Prexasertib Phase II Actionable In a Phase II trial, Prexasertib (LY2606368) treatment resulted in a partial response in 33% (8/24) of BRCA wild-type patients with high-grade serous ovarian cancer (PMID: 29361470; NCT02203513). 29361470
BRCA1 L631Qfs*4 ovarian carcinoma sensitive Rucaparib Clinical Study Actionable In a clinical study, an ovarian carcinoma patient harboring a BRCA1 L631Qfs*4 germline mutation demonstrated a partial response when treated with Rubraca (rucaparib) (PMID: 28588062). 28588062
BRCA1 L392Qfs*5 ovarian carcinoma sensitive Rucaparib Clinical Study Actionable In a clinical study, an ovarian carcinoma patient harboring a BRCA1 L392Qfs*5 germline mutation demonstrated a partial response when treated with Rubraca (rucaparib) (PMID: 28588062). 28588062
BRCA1 loss breast cancer sensitive Carboplatin Phase II Actionable In a Phase II trial, high dose Paraplatin (carboplatin) chemotherapy was more beneficial for breast cancer patients with BRCA1 loss than was conventional anthracycline-based chemotherapy (PMID: 21135055). 21135055
BRCA1 loss breast cancer sensitive Olaparib Preclinical Actionable In a preclinical study, Lynparza (olaparib) treatment resulted in prolonged overall survival in BRCA1 deficient transgenic mouse models of breast cancer (PMID: 27454287). 27454287
BRCA1 loss FGFR2-DNM3 triple-receptor negative breast cancer predicted - sensitive BGJ398 Preclinical - Cell line xenograft Actionable In a preclinical study, BRCA1-deficient triple-receptor negative breast cancer xenograft models harboring FGFR2-DNM3 were sensitive to treatment with BGJ398, demonstrating tumor regression, however, after 43 days on average, three out of six models developed resistance (PMID: 29203461). 29203461
BRCA1 loss FGFR2-DNM3 triple-receptor negative breast cancer sensitive BGJ398 + Talazoparib Preclinical - Cell line xenograft Actionable In a preclinical study, BRCA1-deficient triple-receptor negative breast cancer xenograft models treated with a combination of BGJ398 and Talazoparib (BMN-673) demonstrated a complete response and no relapse within 80 days (PMID: 29203461). 29203461
BRCA1 loss FGFR2-DNM3 triple-receptor negative breast cancer sensitive BGJ398 + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, BRCA1-deficient triple-receptor negative breast cancer xenograft models harboring FGFR2-DNM3 treated with a combination of BGJ398 and Lynparza (olaparib) demonstrated a complete response and did not develop resistance as compared to those models treated with BGJ398 alone (PMID: 29203461). 29203461
BRCA1 loss FGFR2-DNM3 triple-receptor negative breast cancer decreased response Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, BRCA1-deficient triple-receptor negative breast cancer xenograft models treated with BKM120 demonstrated only delayed tumor progression when compared to treatment with BGJ398, which resulted in tumor regression (PMID: 29203461). 29203461
BRCA1 loss TP53 loss breast cancer sensitive AZD2461 Preclinical Actionable In a preclinical study, a breast cancer model lacking both BRCA1 and TP53 demonstrated sensitivity to treatment with AZD2461, which resulted in decreased tumor volume (PMID: 27550455). 27550455
BRCA1 N682* ovarian carcinoma sensitive Rucaparib Clinical Study Actionable In a clinical study, an ovarian carcinoma patient harboring a BRCA1 N682* germline mutation demonstrated a partial response when treated with Rubraca (rucaparib) (PMID: 28588062). 28588062