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Gene Symbol TSC1
Synonyms LAM | TSC
Gene Description TSC1, TSC complex subunit 1, is a tumor suppressor (PMID: 30562755) that forms a complex with Tsc2 and inhibits mTOR pathway signaling, thus regulating cell growth and metabolism (PMID: 27226234). Germline TSC1 inactivating mutations cause tuberous sclerosis complex and somatic TSC1 mutations have been identified in various cancers, including renal cell carcinoma, mucosal melanoma, and breast cancer (PMID: 27226234, PMID: 30327302, PMID: 29185092, PMID: 28027327).
ACMG Incidental List v3.0:
Yes, Tuberous sclerosis complex (PMID: 34012068)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1070V missense unknown TSC1 A1070V does not lie within any known functional domains of the Tsc1 protein (UniProt.org). A1070V has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A1072V missense unknown TSC1 A1072V does not lie within any known functional domains of the Tsc1 protein (UniProt.org). A1072V has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A173V missense unknown TSC1 A173V does not lie within any known functional domains of the Tsc1 protein (UniProt.org). A173V has been identified in sequencing studies (PMID: 30578357), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A529S missense unknown TSC1 A529S lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). A529S has been identified in sequencing studies (PMID: 31874108), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A529V missense unknown TSC1 A529V lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). A529V has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A567V missense no effect - predicted TSC1 A567V lies within the WDR45B-interacting region of the Tsc1 protein (UniProt.org). A567V demonstrates similar mTOR pathway inhibition as wild-type Tsc1 in cell culture (PMID: 22161988), and therefore, is predicted to have no effect on Tsc1 protein function.
A944T missense unknown TSC1 A944T lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). A944T has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
A944V missense unknown TSC1 A944V lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). A944V has been identified in sequencing studies (PMID: 22495314), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
C165Y missense unknown TSC1 C165Y does not lie within any known functional domains of the Tsc1 protein (UniProt.org). C165Y has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
C197F missense unknown TSC1 C197F does not lie within any known functional domains of the Tsc1 protein (UniProt.org). C197F has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
D239G missense unknown TSC1 D239G does not lie within any known functional domains of the Tsc1 protein (UniProt.org). D239G has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
D291Lfs*22 frameshift loss of function - predicted TSC1 D291Lfs*22 indicates a shift in the reading frame starting at amino acid 291 and terminating 22 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). D291Lfs*22 has not been characterized however, due to the effects of other truncation mutations downstream of D291 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
D47G missense unknown TSC1 D47G does not lie within any known functional domains of the Tsc1 protein (UniProt.org). D47G has been identified in sequencing studies (PMID: 20668451), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
D47N missense unknown TSC1 D47N does not lie within any known functional domains of the Tsc1 protein (UniProt.org). D47N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
del deletion loss of function TSC1 del indicates a deletion of the TSC1 gene.
E636fs frameshift loss of function - predicted TSC1 E636fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 636 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). E636fs has not been characterized however, due to the effects of other truncation mutations downstream of E636 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
E78* nonsense loss of function - predicted TSC1 E78* results in a premature truncation of the Tsc1 protein at amino acid 78 of 1164 (UniProt.org). E78* has not been characterized however, due to the effects of other truncation mutations downstream of E78 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
E876K missense unknown TSC1 E876K lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). E876K has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
E931D missense unknown TSC1 E931D lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). E931D has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
F158C missense unknown TSC1 F158C does not lie within any known functional domains of the Tsc1 protein (UniProt.org). F158C results in reduced protein stability in culture (PMID: 18397877), but has not been fully biochemically characterized and therefore, its effect on Tsc1 protein function is unknown.
F188S missense unknown TSC1 F188S does not lie within any known functional domains of the Tsc1 protein (UniProt.org). F188S has been identified in the scientific literature (PMID: 35171658), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Oct 2022).
F216* nonsense loss of function - predicted TSC1 F216* results in a premature truncation of the Tsc1 protein at amino acid 216 of 1164 (UniProt.org). F216* has not been characterized however, due to the effects of other truncation mutations downstream of F216 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
F216A missense unknown TSC1 F216A does not lie within any known functional domains of the Tsc1 protein (UniProt.org). F216A results in altered subcellular localization but interaction with Tsc2 similar to wild-type Tsc1 and attenuates mTor signaling in cultured cells (PMID: 18397877), and therefore, its effect on Tsc1 protein function is unknown.
F216Dfs*3 frameshift loss of function - predicted TSC1 F216Dfs*3 indicates a shift in the reading frame starting at amino acid 216 and terminating 3 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). F216Dfs*3 has not been characterized however, due to the effects of other truncation mutations downstream of F216 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
G1035S missense no effect TSC1 G1035S does not lie within any known functional domains of the Tsc1 protein (UniProt.org). G1035S demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in cell culture (PMID: 18830229).
G305A missense unknown TSC1 G305A does not lie within any known functional domains of the Tsc1 protein (UniProt.org). G305A has been identified in sequencing studies (PMID: 18830229) , but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
G305R missense unknown TSC1 G305R does not lie within any known functional domains of the Tsc1 protein (UniProt.org). G305R demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in culture, but the nucleotide change is predicted to be pathogenic and affect RNA splicing (PMID: 18830229).
G305W missense unknown TSC1 G305W does not lie within any known functional domains of the Tsc1 protein (UniProt.org). G305W demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in culture, but the nucleotide change is predicted to be pathogenic and affect RNA splicing (PMID: 18830229).
G382D missense unknown TSC1 G382D does not lie within any known functional domains of the Tsc1 protein (UniProt.org). G382D has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
H105R missense unknown TSC1 H105R does not lie within any known functional domains of the Tsc1 protein (UniProt.org). H105R results in interaction with Tsc2 similar to wild-type Tsc1 and attenuates mTor signaling in culture, however, the genomic change may lead to aberrant splicing (PMID: 18397877), and therefore, its effect on Tsc1 protein function is unknown.
H181Y missense unknown TSC1 H181Y does not lie within any known functional domains of the Tsc1 protein (UniProt.org). H181Y has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
H206D missense unknown TSC1 H206D does not lie within any known functional domains of the Tsc1 protein (UniProt.org). H206D results in reduced protein stability in culture (PMID: 18397877), but has not been fully biochemically characterized and therefore, its effect on Tsc1 protein function is unknown.
H68R missense unknown TSC1 H68R does not lie within any known functional domains of the Tsc1 protein (UniProt.org). H68R results in reduced protein stability in culture (PMID: 18397877), but has not been fully biochemically characterized and therefore, its effect on Tsc1 protein function is unknown.
inact mut unknown loss of function TSC1 inact mut indicates that this variant results in a loss of function of the Tsc1 protein. However, the specific amino acid change has not been identified.
K477* nonsense loss of function - predicted TSC1 K477* results in a premature truncation of the Tsc1 protein at amino acid 477 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), K477* is predicted to lead to a loss of Tsc1 protein function.
K477N missense unknown TSC1 K477N lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). K477N has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
K82T missense no effect TSC1 K82T does not lie within any known functional domains of the Tsc1 protein (UniProt.org). K82T demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in cell culture (PMID: 21309039).
L116fs frameshift loss of function - predicted TSC1 L116fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 116 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of most known functional domains (UniProt.org), L116fs is predicted to lead to a loss of Tsc1 protein function.
L117P missense loss of function TSC1 L117P does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L117P confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
L129H missense unknown TSC1 L129H does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L129H has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
L180P missense loss of function TSC1 L180P does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L180P confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
L191H missense loss of function TSC1 L191H does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L191H confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
L203fs frameshift loss of function - predicted TSC1 L203fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 203 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), L203fs is predicted to lead to a loss of Tsc1 protein function.
L557Cfs*72 frameshift loss of function - predicted TSC1 L557Cfs*72 indicates a shift in the reading frame starting at amino acid 557 and terminating 72 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), L557Cfs*72 is predicted to lead to a loss of Tsc1 protein function.
L72R missense unknown TSC1 L72R does not lie within any known functional domains of the Tsc1 protein (UniProt.org). L72R has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
L87* nonsense loss of function - predicted TSC1 L87* results in a premature truncation of the Tsc1 protein at amino acid 87 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), L87* is predicted to lead to a loss of Tsc1 protein function.
L896F missense unknown TSC1 L896F lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). L896F has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
L896V missense unknown TSC1 L896V lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). L896V has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
LOH deletion unknown TSC1 LOH indicates the loss of one parental copy of the TSC1 gene, resulting in loss of heterozygosity.
loss unknown loss of function TSC1 loss indicates loss of the TSC1 gene, mRNA, and protein.
M18Cfs*8 frameshift loss of function - predicted TSC1 M18Cfs*8 indicates a shift in the reading frame starting at amino acid 18 and terminating 8 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), M18Cfs*8 is predicted to lead to a loss of Tsc1 protein function.
M18fs frameshift loss of function - predicted TSC1 M18fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 18 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), M18fs is predicted to lead to a loss of Tsc1 protein function.
M194Afs*13 frameshift loss of function - predicted TSC1 M194Afs*13 indicates a shift in the reading frame starting at amino acid 194 and terminating 13 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). M194Afs*13 has not been characterized however, due to the effects of other truncation mutations downstream of M194 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
M224R missense loss of function TSC1 M224R does not lie within any known functional domains of the Tsc1 protein (UniProt.org). M224R confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
M271T missense unknown TSC1 M271T (corresponds to M318T in the canonical isoform) does not lie within any known functional domains of the Tsc1 protein (UniProt.org). M271T has been identified in sequencing studies (PMID: 25528188, PMID: 30719144, PMID: 28839440), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
M322T missense unknown TSC1 M322T does not lie within any known functional domains of the Tsc1 protein (UniProt.org). M322T has been identified in the scientific literature (PMID: 29185092, PMID: 9803264, PMID: 9328481), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
M322V missense unknown TSC1 M322V does not lie within any known functional domains of the Tsc1 protein (UniProt.org). M322V has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
mutant unknown unknown TSC1 mutant indicates an unspecified mutation in the TSC1 gene.
N198_F199delinsI indel loss of function TSC1 N198_F199delinsI results in the deletion of an asparagine (N) and a phenylalanine (F) from aa 198 to 199 of the Tsc1 protein, combined with the insertion of an isoleucine (I) at the same location (UniProt.org). N198_F199delinsI confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
N762S missense unknown TSC1 N762S lies within the coiled-coiled domain of the Tsc1 protein (UniProt.org). N762S has not been characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
N891fs frameshift unknown TSC1 N891fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 891 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). N891fs has been identified in the scientific literature (PMID: 28423702, PMID: 29636988), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
P1143L missense unknown TSC1 P1143L does not lie within any known functional domains of the Tsc1 protein (UniProt.org). P1143L has been identified in sequencing studies (PMID: 27023146, PMID: 19789314), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
P141S missense unknown TSC1 P141S does not lie within any known functional domains of the Tsc1 protein (UniProt.org). P141S has not been characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
P590S missense unknown TSC1 P590S lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). P590S has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
P602Sfs*4 frameshift loss of function - predicted TSC1 P602Sfs*4 indicates a shift in the reading frame starting at amino acid 602 and terminating 4 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). P602Sfs*4 has not been characterized however, due to the effects of other truncation mutations downstream of P602 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
Q413* nonsense loss of function - predicted TSC1 Q413* results in a premature truncation of the Tsc1 protein at amino acid 413 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Q413* is predicted to lead to a loss of Tsc1 protein function.
Q413Rfs*27 frameshift loss of function - predicted TSC1 Q413Rfs*27 indicates a shift in the reading frame starting at amino acid 413 and terminating 27 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). Q413Rfs*27 has not been characterized however, due to the effects of other truncation mutations downstream of Q413 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
Q516* nonsense loss of function - predicted TSC1 Q516* results in a premature truncation of the Tsc1 protein at amino acid 516 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Q516* is predicted to lead to loss of Tsc1 protein function.
Q55Sfs*7 frameshift loss of function - predicted TSC1 Q55Sfs*7 indicates a shift in the reading frame starting at amino acid 55 and terminating 7 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Q55Sfs*7 is predicted to lead to a loss of Tsc1 protein function.
Q654E missense unknown TSC1 Q654E lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). Q654E has been identified in sequencing studies (PMID: 10570911), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R1027Q missense unknown TSC1 R1027Q does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R1027Q has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R1062W missense unknown TSC1 R1062W does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R1062W has been identified in the scientific literature (PMID: 20165957) but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R1097C missense unknown TSC1 R1097C does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R1097C has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
R1097H missense no effect TSC1 R1097H does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R1097H demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in cell culture (PMID: 18830229).
R190P missense loss of function - predicted TSC1 R190P does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R190P is predicted to result in a loss of Tsc1 protein function in computational analyses, and results in decreased Tsc1 protein expression as a result of proteosomal degradation in cell culture (PMID: 19747374), and therefore, is predicted to result in a loss of Tsc1 protein function.
R204C missense loss of function TSC1 R204C does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R204C results in a loss of Tsc1 binding to Tsc2 and increased phosphorylation of S6k in cell culture (PMID: 28215400).
R204H missense unknown TSC1 R204H does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R204H has been identified in sequencing studies (PMID: 25303977), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R204L missense unknown TSC1 R204L does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R204L has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
R228Q missense unknown TSC1 R228Q does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R228Q has been identified in the scientific literature (PMID: 28481359) but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R22W missense loss of function TSC1 R22W does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R22W results in a loss of Tsc1 binding to Tsc2 and increased phosphorylation of S6k in cell culture (PMID: 28215400).
R245* nonsense loss of function - predicted TSC1 R245* results in a premature truncation of the Tsc1 protein at amino acid 245 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R245* is predicted to lead to a loss of Tsc1 protein function.
R246K missense unknown TSC1 R246K does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R246K demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in culture, however, the nucleotide change occurs at a splice site and is predicted to result in an RNA splicing defect (PMID: 18830229), and therefore, its effect on Tsc1 protein function is unknown.
R284H missense unknown TSC1 R284H does not lie within any known functional domains of the Tsc1 protein (UniProt.org). R284H has been identified in the scientific literature (PMID: 31978326, PMID: 27127140), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
R424fs frameshift loss of function - predicted TSC1 R424fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 424 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R424fs is predicted to lead to a loss of Tsc1 protein function.
R500* nonsense loss of function - predicted TSC1 R500* results in a premature truncation of the Tsc1 protein at amino acid 500 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R500* is predicted to lead to a loss of Tsc1 protein function.
R509* nonsense loss of function - predicted TSC1 R509* results in a premature truncation of the Tsc1 protein at amino acid 509 of 1164 (UniProt.org). R509* has not been characterized however, due to the effects of other truncation mutations downstream of R509 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
R509Q missense no effect TSC1 R509Q lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). R509Q demonstrates protein stability and mTOR pathway inhibition similar to wild-type Tsc1 in cell culture (PMID: 18830229).
R692* nonsense loss of function TSC1 R692* results in a premature truncation of the Tsc1 protein at amino acid 692 of 1164 (UniProt.org). R692* results in decreased binding to Tsc2 (PMID: 20547222) and loss of Tsc1 protein expression in cell culture (PMID: 23401075).
R706C missense unknown TSC1 R706C lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). R706C has been identified in the scientific literature (PMID: 28481359) but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R706H missense unknown TSC1 R706H lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). R706H has been identified in the scientific literature (PMID: 28481359) but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R786Q missense unknown TSC1 R786Q lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). R786Q has been identified in sequencing studies (PMID: 25096233), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
R98* nonsense loss of function - predicted TSC1 R98* results in a premature truncation of the Tsc1 protein at amino acid 98 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), R98* is predicted to lead to a loss of Tsc1 protein function.
S1043del deletion unknown TSC1 S1043del results in the deletion of an amino acid in a poly-serine region of the Tsc1 protein at amino acid 1043 (UniProt.org). S1043del has been identified in the scientific literature (PMID: 30429033), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jul 2022).
S1043dup duplication unknown TSC1 S1043dup indicates the insertion of the duplicate amino acid, serine (S)-1043, in the Tsc1 protein (UniProt.org). S1043dup results in reduced protein stability (PMID: 34739309), but has not been fully biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
S1043fs frameshift unknown TSC1 S1043fs results in a change in the amino acid sequence of the Tsc1 protein beginning at aa 1043 of 1164, likely resulting in premature truncation of the functional protein (UniProt.org). S1043fs has been identified in the scientific literature (PMID: 31978326, PMID: 35085982), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
S1043N missense unknown TSC1 S1043N does not lie within any known functional domains of the Tsc1 protein (UniProt.org). S1043N has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
S16C missense unknown TSC1 S16C does not lie within any known functional domains of the Tsc1 protein (UniProt.org). S16C has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
S282* nonsense loss of function - predicted TSC1 S282* results in a premature truncation of the Tsc1 protein at amino acid 282 of 1164 (UniProt.org). S282* has not been characterized however, due to the effects of other truncation mutations downstream of S282 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
S331Efs*10 frameshift loss of function - predicted TSC1 S331Efs*10 indicates a shift in the reading frame starting at amino acid 331 and terminating 10 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), S331Efs*10 is predicted to lead to a loss of Tsc1 protein function.
S35C missense unknown TSC1 S35C does not lie within any known functional domains of the Tsc1 protein (UniProt.org). S35C results in interaction with Tsc2 and subcellular localization similar to wild-type Tsc1 and attenuates mTor signaling in culture, however, the genomic change may lead to aberrant splicing (PMID: 18397877), and therefore, its effect on Tsc1 protein function is unknown.
S35Q missense unknown TSC1 S35Q does not lie within any known functional domains of the Tsc1 protein (UniProt.org). S35Q has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
S361Y missense unknown TSC1 S361Y does not lie within any known functional domains of the Tsc1 protein (UniProt.org). S361Y has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
S410* nonsense loss of function - predicted TSC1 S410* results in a premature truncation of the Tsc1 protein at amino acid 410 of 1164 (UniProt.org). S410* has not been characterized however, due to the effects of other truncation mutations downstream of S410 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
S575F missense unknown TSC1 S575F lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). S575F has been identified in sequencing studies (PMID: 30348637), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
S661N missense unknown TSC1 S661N lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). S661N has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Jun 2022).
T417I missense no effect TSC1 T417I lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). T417I demonstrates cellular localization, binding to Tsc2, and inhibition of S6 phosphorylation similar to wild-type Tsc1 in culture (PMID: 18397877).
V128del deletion loss of function TSC1 V128del results in the deletion of an amino acid of the Tsc1 protein at aa 128 (UniProt.org). V128del confers a loss of function on the Tsc1 protein as indicated by decreased Tsc1 protein expression and loss of mTOR pathway inhibition in cell culture (PMID: 18830229).
V220F missense unknown TSC1 V220F does not lie within any known functional domains of the Tsc1 protein (UniProt.org). V220F has been identified in the scientific literature (PMID: 22923433), but has not been biochemically characterized and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
V46Wfs*16 frameshift loss of function - predicted TSC1 V46Wfs*16 indicates a shift in the reading frame starting at amino acid 46 and terminating 16 residues downstream causing a premature truncation of the 1164 amino acid Tsc1 protein (UniProt.org). V46Wfs*16 has not been characterized however, due to the effects of other truncation mutations downstream of V46 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
V497L missense unknown TSC1 V497L lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). V497L has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Sep 2022).
V620A missense unknown TSC1 V620A lies within the region of the Tsc1 protein that mediates interaction with WDR45B (UniProt.org). V620A has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
V858L missense unknown TSC1 V858L lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). V858L has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
W164* nonsense loss of function - predicted TSC1 W164* results in a premature truncation of the Tsc1 protein at amino acid 164 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), W164* is predicted to lead to loss of Tsc1 protein function.
W347L missense unknown TSC1 W347L does not lie within any known functional domains of the Tsc1 protein (UniProt.org). W347L has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).
wild-type none no effect Wild-type TSC1 indicates that no mutation has been detected within the TSC1 gene.
Y185* nonsense loss of function - predicted TSC1 Y185* results in a premature truncation of the Tsc1 protein at amino acid 185 of 1164 (UniProt.org). Due to the loss of all known functional domains (UniProt.org), Y185* is predicted to lead to a loss of Tsc1 protein function.
Y312* nonsense loss of function - predicted TSC1 Y312* results in a premature truncation of the Tsc1 protein at amino acid 312 of 1164 (UniProt.org). Y312* has not been characterized however, due to the effects of other truncation mutations downstream of Y312 (PMID: 11875047, PMID: 20547222), is predicted to lead to a loss of Tsc1 protein function.
Y948F missense unknown TSC1 Y948F lies within the coiled-coil domain of the Tsc1 protein (UniProt.org). Y948F has not been characterized in the scientific literature and therefore, its effect on Tsc1 protein function is unknown (PubMed, Nov 2022).