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Gene Symbol TSC2
Synonyms LAM | PPP1R160 | TSC4
Gene Description TSC2, TSC complex subunit 2, forms a complex with Tsc1 and inhibits mTOR pathway signaling, thus regulating cell growth and metabolism (PMID: 27226234). Germline TSC2 inactivating mutations cause tuberous sclerosis complex and somatic TSC2 mutations have been identified in various cancers, including renal cell carcinoma, sarcoma, and breast cancer (PMID: 27226234, PMID: 30303819, PMID: 28860410, 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
A1003fs frameshift loss of function TSC2 A1003fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1003 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). A1003fs confers a loss of function to the Tsc2 protein as indicated by increased Ofd1 and p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
A1110T missense unknown TSC2 A1110T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1110T has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
A1141T missense unknown TSC2 A1141T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1141T has been identified in sequencing studies (PMID: 25724664), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
A1258R missense unknown TSC2 A1258R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1258R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
A1294V missense unknown TSC2 A1294V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1294V has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
A1297T missense unknown TSC2 A1297T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A1297T has been identified in sequencing studies (PMID: 27930734), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
A1719T missense unknown TSC2 A1719T lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). A1719T has been identified in sequencing studies (PMID: 31308077), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
A210T missense unknown TSC2 A210T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A210T has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
A272T missense unknown TSC2 A272T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A272T has been identified in sequencing studies (PMID: 29937994), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
A289V missense unknown TSC2 A289V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A289V has been identified in sequencing studies (PMID: 26806567), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
A460T missense no effect - predicted TSC2 A460T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A460T results in S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 21309039), and therefore, is predicted to have no effect on Tsc2 protein function.
A607E missense loss of function TSC2 A607E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607E results in the loss of repression of Mtorc1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
A607T missense no effect TSC2 A607T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607T demonstrates hamartin interaction, Rheb activation, and inhibition of S6K and S6 phosphorylation to similar levels of wild-type Tsc2 in culture (PMID: 15483652).
A607V missense unknown TSC2 A607V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A607V has been identified in sequencing studies (PMID: 26806567, PMID: 26343384), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
A678T missense unknown TSC2 A678T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). A678T has been identified in sequencing studies (PMID: 29642553, PMID: 31176623), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
A84T missense no effect - predicted TSC2 A84T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A84T results in Tsc2 splicing similar to wild-type Tsc2 in an in vitro assay and complex formation with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
A86T missense unknown TSC2 A86T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). A86T has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
amp none no effect TSC2 amplification indicates an increased number of copies of the TSC2 gene. However, the mechanism causing the increase is unspecified.
C256Y missense unknown TSC2 C256Y lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). C256Y has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
C811R missense unknown TSC2 C811R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). C811R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
D1004N missense unknown TSC2 D1004N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1004N has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
D1004Y missense unknown TSC2 D1004Y does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1004Y has been identified in sequencing studies (PMID: 30556601), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
D1406N missense unknown TSC2 D1406N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). D1406N has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
D1512A missense loss of function TSC2 D1512A (corresponding to D1535A in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1512A results in the loss of repression of Mtorc1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
D1590N missense unknown TSC2 D1590N lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1590N has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
D1598fs frameshift loss of function - predicted TSC2 D1598fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1598 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). D1598fs has not been characterized, however, due to the effects of other truncation mutations downstream of D1598 (PMID: 22903760, PMID: 26703369), is predicted to lead to a loss of Tsc2 protein function.
D1656N missense no effect TSC2 D1656N lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1656N results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay (PMID: 32502382), inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382, PMID: 31799751), and interaction with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751).
D1656Y missense no effect - predicted TSC2 D1656Y lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). D1656Y results in noncanonical splicing of Tsc2 in cultured cells (PMID: 31799751), but protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay (PMID: 32502382), inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382, PMID: 31799751), and interaction with Tsc1 similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
D1690fs frameshift loss of function - predicted TSC2 D1690fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1690 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). D1690fs has not been characterized however, due to the effects of other truncation mutations downstream of D1690 (PMID: 22903760, PMID: 26703369), is predicted to lead to a loss of Tsc2 protein function.
E1343D missense unknown TSC2 E1343D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). E1343D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
E134K missense unknown TSC2 E134K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E134K has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
E379G missense unknown TSC2 E379G lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E379G has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
E546K missense unknown TSC2 E546K does not lie within any known functional domains of the Tsc2 protein (UniProt.org). E546K has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
E652fs frameshift loss of function - predicted TSC2 E652fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 652 of 766, likely resulting in premature truncation of the functional protein (UniProt.org). E652fs has not been characterized however, due to the effects of other truncation mutations downstream of E652 (PMID: 22903760, PMID: 26703369, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
E74K missense unknown TSC2 E74K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). E74K has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
E96* nonsense loss of function - predicted TSC2 E96* results in a premature truncation of the Tsc2 protein at amino acid 96 of 1807 (UniProt.org). E96* has not been characterized however, due to the effects of other truncation mutations downstream of E96 (PMID: 22903760, PMID: 26703369, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
F1510del deletion unknown TSC2 F1510del results in the deletion of an amino acid of the Tsc2 protein at amino acid 1510 (UniProt.org). F1510del has been identified in sequencing studies (PMID: 29461635, PMID: 25231023), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
F15V missense unknown TSC2 F15V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). F15V has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
F1668L missense loss of function - predicted TSC2 F1668L lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). F1668L results in protein stability and inhibition of Mtorc1 signaling similar to wild-type Tsc2 in cultured cells but results in a loss of catalytic activity in an in vitro assay (PMID: 32502382), and therefore, is predicted to result in a loss of Tsc2 protein function.
F452L missense unknown TSC2 F452L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). F452L has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
G1055D missense unknown TSC2 G1055D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1055D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
G1354D missense unknown TSC2 G1354D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1354D has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
G1416D missense no effect - predicted TSC2 G1416D (corresponding to G1439D in the canonical isoform) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1416D results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
G1494D missense unknown TSC2 G1494D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1494D has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
G150K missense unknown TSC2 G150K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G150K has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, May 2021).
G1544V missense loss of function TSC2 G1544V (corresponding to G1567V in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). G1544V results in the loss of repression of MTORC1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
G1791S missense unknown TSC2 G1791S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G1791S has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
G294E missense loss of function TSC2 G294E lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G294E results in increased expression of Mcp-1 compared to wild-type Tsc2 in cell culture (PMID: 16129702) and failure to bind TSC1 in vitro (PMID: 11741833, PMID: 23955302).
G305* nonsense loss of function - predicted TSC2 G305* results in a premature truncation of the Tsc2 protein at amino acid 305 of 1807 (UniProt.org). G305* has not been characterized, however, due to the effects of other truncation mutations downstream of G305 (PMID: 22903760, PMID: 26703369, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
G440S missense unknown TSC2 G440S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G440S has been identified in sequencing studies (PMID: 10205261), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
G62E missense no effect - predicted TSC2 G62E lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). G62E results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
G676S missense unknown TSC2 G676S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). G676S has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
H1135R missense unknown TSC2 H1135R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). H1135R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
H1617Y missense loss of function TSC2 H1617Y (corresponding to H1640Y in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). H1617Y results in the loss of repression of Mtorc1 as indicated by assays that demonstrate increased phosphorylation of S6k in cultured cells (PMID: 18854862).
H1718P missense loss of function TSC2 H1718P lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). H1718P confers a loss of function to the Tsc2 protein as indicated by increased Ofd1 and p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
H1746_R1751del deletion loss of function TSC2 H1746_R1751del results in the deletion of six amino acids in the Rap-GAP domain of the Tsc2 protein from amino acids 1746 to 1751 (UniProt.org). H1746_R1751del confers a loss of function on the Tsc2 protein as indicated by destabilization of the TSC1-TSC2 complex (PMID: 21309039), increased phosphorylation of S6, potentially resulting in hyperactivation of Mtorc1, and a decrease in Akt phosphorylation in cultured cells. (PMID: 31591157).
H597N missense unknown TSC2 H597N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). H597N has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
I1197F missense loss of function - predicted TSC2 I1197F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). I1197F results in interaction with Tsc1 similar to wild-type Tsc2, but decreased inhibition of mTorc1 activity as indicated by reduced inhibition of S6k phosphorylation in cultured cells (PMID: 31799751), and therefore, is predicted to result in a loss of Tsc2 protein function.
I365del deletion loss of function TSC2 I365del results in the deletion of an amino acid in the Tsc2 protein at amino acid 365 (UniProt.org). I365del confers a loss of function on Tsc2, as demonstrated by abolished tuberin-hamartin binding in a yeast assay (PMID: 11741833), and failure to inhibit Mcp-1 production in cell culture (PMID: 16129702).
I427_S428del deletion unknown TSC2 I427_S428del results in the deletion of two amino acids of the Tsc2 protein from amino acid 427 to 428 (UniProt.org). I427_S428del has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
inact mut unknown loss of function TSC2 inact mut indicates that this variant results in a loss of function of the Tsc2 protein. However, the specific amino acid change has not been identified.
K1065E missense unknown TSC2 K1065E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). K1065E has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
K1585R missense unknown TSC2 K1585R lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). K1585R has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
K347Efs*36 frameshift loss of function - predicted TSC2 K347Efs*36 indicates a shift in the reading frame starting at amino acid 347 and terminating 36 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). K347Efs*36 results in increased phosphorylation of S6k1 and Stat3 in cultured cells (PMID: 31454656), and therefore, is predicted to lead to a loss of Tsc2 protein function.
L1137F missense unknown TSC2 L1137F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1137F has not been characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
L1198M missense unknown TSC2 L1198M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1198M has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
L1216I missense unknown TSC2 L1216I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1216I has not been characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
L1504F missense unknown TSC2 L1504F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L1504F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
L1750Afs*25 frameshift loss of function - predicted TSC2 L1750Afs*25 indicates a shift in the reading frame starting at amino acid 1750 and terminating 25 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). L1750Afs*25 results in increased mTorc1 signaling in culture (PMID: 22903760), and therefore, is predicted to result in a loss of Tsc2 protein function.
L204V missense unknown TSC2 L204V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L204V has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
L369P missense loss of function TSC2 L369P lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L369P fails to inhibit mTorc1 activity as indicated by reduced inhibition of S6k phosphorylation and results in decreased binding to Tsc1 in cultured cells (PMID: 31799751).
L369R missense unknown TSC2 L369R lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). L369R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
L493V missense unknown TSC2 L493V does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L493V results in decreased interaction with Tsc1 in cultured cells, and noncanonical Tsc2 splicing in an in vitro assay, but results in Mtorc1 inhibition similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, its effect on Tsc2 protein function is unknown.
L604P missense unknown TSC2 L604P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L604P has been identified in sequencing studies (PMID: 26469692), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
L688M missense unknown TSC2 L688M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L688M has been identified in sequencing studies (PMID: 30503610), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2021).
L916P missense loss of function - predicted TSC2 L916P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). L916P results in interaction with Tsc1 similar to wild-type Tsc2, but fails to inhibit Mtorc1 activity as indicated by failure to inhibit S6k phosphorylation in cultured cells (PMID: 31799751), and therefore, is predicted to lead to a loss of Tsc2 protein function.
loss unknown loss of function TSC2 loss indicates loss of the TSC2 gene, mRNA, and protein.
M168I missense unknown TSC2 M168I lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M168I has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
M1691T missense unknown TSC2 M1691T lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). M1691T has been identified in sequencing studies (PMID: 27882345), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
M280T missense loss of function TSC2 M280T lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M280T results in disruption of the Tsc complex function as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
M286V missense no effect - predicted TSC2 M286V lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). M286V results in the expression of Mcp-1 similar to wild-type Tsc2 in cell culture (PMID: 16129702) and binds Tsc1 similar to wild-type Tsc2 in an in vitro assay (PMID: 11741833), and therefore, is predicted to have no effect on Tsc2 protein function.
M649I missense unknown TSC2 M649I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). M649I has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
mutant unknown unknown TSC2 mutant indicates an unspecified mutation in the TSC2 gene.
N1214I missense unknown TSC2 N1214I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). N1214I has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
N1224I missense unknown TSC2 N1224I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). N1224I has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
N1643H missense loss of function TSC2 N1643H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). N1643H demonstrates protein stability similar to wild-type Tsc2 in an in vitro assay, but fails to inhibit Mtorc1 signaling and results in a loss of catalytic activity in an in vitro assay (PMID: 32502382), and therefore, results in a loss of Tsc2 protein function.
N1707S missense no effect - predicted TSC2 N1707S lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). N1707S results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay and inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382), and therefore, is predicted to have no effect on Tsc2 protein function.
N275del deletion loss of function TSC2 N275del results in the deletion of an amino acid in the TSC1-interacting region of the Tsc1 protein at amino acid 275 (UniProt.org). N275del results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
P1092L missense unknown TSC2 P1092L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1092L has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
P1292A missense no effect - predicted TSC2 P1292A (corresponding to P1315A in the canonical isoform) does not lie within any known functional domains of the Tsc1 protein (UniProt.org). P1292A results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
P1521T missense unknown TSC2 P1521T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1521T has been identified in the scientific literature (PMID: 31978326), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
P1770S missense unknown TSC2 P1770S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P1770S has been identified in sequencing studies (PMID: 24265153), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
P237L missense unknown TSC2 P237L lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). P237L has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
P674S missense unknown TSC2 P674S does not lie within any known functional domains of the Tsc2 protein (UniProt.org). P674S has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
Q1178* nonsense loss of function - predicted TSC2 Q1178* results in a premature truncation of the Tsc2 protein at amino acid 1178 of 1807 (UniProt.org). Q1178* has not been characterized however, due to the effects of other truncation mutations downstream of Q1178 (PMID: 22903760, PMID: 26703369), is predicted to lead to a loss of Tsc2 protein function.
Q1192* nonsense loss of function - predicted TSC2 Q1192* results in a premature truncation of the Tsc2 protein at amino acid 1192 of 1807 (UniProt.org). Q1192* has not been characterized however, due to the effects of other truncation mutations downstream of Q1192 (PMID: 22903760, PMID: 26703369), is predicted to lead to a loss of Tsc2 protein function.
Q371H missense unknown TSC2 Q371H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). Q371H has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
Q373P missense no effect - predicted TSC2 Q373P lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). Q373P results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
Q572H missense unknown TSC2 Q572H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). Q572H has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1032Q missense unknown TSC2 R1032Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1032Q has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
R115H missense unknown TSC2 R115H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R115H has been identified in sequencing studies (PMID: 29312904), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1268G missense unknown TSC2 R1268G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1268G has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
R1329P missense unknown TSC2 R1329P does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1329P has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
R1361Q missense unknown TSC2 R1361Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1361Q has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1409G missense no effect - predicted TSC2 R1409G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1409G results in canonical splicing in an in vitro assay, and leads to Tsc1 interaction and Mtorc1 inhibition similar to wild-type Tsc2 in cultured cells (PMID: 31799751), and therefore, is predicted to have no effect on Tsc2 protein function.
R1580W missense no effect - predicted TSC2 R1580W lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1580W results in protein stability and enzymatic activity similar to wild-type Tsc2 in an in vitro assay, and inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells (PMID: 32502382), and therefore, is predicted to have no effect on Tsc2 protein function.
R1639H missense unknown TSC2 R1639H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1639H has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1720Q missense loss of function TSC2 R1720Q (corresponding to R1743Q in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1720Q results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
R1729H missense unknown TSC2 R1729H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1729H has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
R1743W missense loss of function TSC2 R1743W lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1743W results in the loss of repression of mTORC1 as demonstrated by increased phosphorylation of S6K1 and 4E-BP1, reduced intrinsic GTPase activity, and PEX5 association and peroxisomal localization compared to wild-type Tsc2 protein in in-vitro assays (PMID: 23955302).
R1745C missense unknown TSC2 R1745C lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1745C has been identified in sequencing studies (PMID: 29669935, PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1745H missense unknown TSC2 R1745H lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1745H has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R1795C missense no effect TSC2 R1795C (corresponding to R1772C in isoform 4) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R1795C demonstrates activity similar to wild-type Tsc2 in in vitro assays (PMID: 21309039, PMID: 18302728).
R308W missense loss of function TSC2 R308W lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R308W fails to inhibit Mtorc1 activity as indicated by reduced inhibition of S6k phosphorylation and results in decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
R367Q missense no effect - predicted TSC2 R367Q lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R367Q results in the expression of Mcp-1 similar to wild-type Tsc2 in cell culture (PMID: 16129702) and binds TSC1 similar to wild-type in an in vitro assay (PMID: 11741833), and therefore, is predicted to have no effect on Tsc2 protein function.
R537C missense unknown TSC2 R537C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R537C has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Sep 2021).
R57H missense unknown TSC2 R57H lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R57H results in reduced expression of Tsc1 and Tsc2, however, also demonstrates increased S6k phosphorylation compared to wild-type Tsc2 in cultured cells (PMID: 21309039), and therefore, its effect on Tsc2 protein function is unknown.
R585H missense unknown TSC2 R585H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R585H has been identified in sequencing studies (PMID: 27149842, PMID: 22490766) but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R611Q missense loss of function TSC2 R611Q does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R611Q fails to inhibit Mtorc1 signaling in cultured cells (PMID: 31799751, PMID: 26703369, PMID: 18854862), and results in reduced interaction with Tsc1 in cultured cells (PMID: 26703369, PMID: 18854862).
R622W missense loss of function TSC2 R622W does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R622W confers a loss of function to the Tsc2 protein as it results in loss of Tsc1 binding and decreased Tsc2 GAP activity in cell culture (PMID: 20633017).
R718H missense unknown TSC2 R718H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R718H has been identified in sequencing studies (PMID: 25233892, PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R901C missense unknown TSC2 R901C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R901C has been identified in sequencing studies (PMID: 27095580, PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R901H missense unknown TSC2 R901H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R901H has been identified in sequencing studies (PMID: 29899868), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R905fs frameshift loss of function TSC2 R905fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 905 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). R905fs confers a loss of function to the Tsc2 protein as indicated by increased p62 expression associated with decreased autophagy, and reduced ciliogenesis in patient samples (PMID: 29937275).
R978H missense unknown TSC2 R978H does not lie within any known functional domains of the Tsc2 protein (UniProt.org). R978H has been identified in sequencing studies (PMID: 25822088, PMID: 22343534), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
R98W missense loss of function TSC2 R98W lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). R98W results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
S1036F missense unknown TSC2 S1036F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1036F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S1045F missense loss of function - predicted TSC2 S1045F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1045F retains the ability to form TSC complex, but results in reduced ability to inhibit S6k phosphorylation in culture (PMID: 31799751), and therefore, is predicted to lead to a loss of Tsc2 protein function.
S1085fs frameshift loss of function - predicted TSC2 S1085fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 1085 of 1807, likely resulting in premature truncation of the functional protein (UniProt.org). S1085fs has not been characterized however, due to the effects of other truncation mutations downstream of S1085 (PMID: 22903760, PMID: 26703369), is predicted to lead to a loss of Tsc2 protein function.
S1090C missense unknown TSC2 S1090C does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1090C has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Jun 2021).
S1130A missense unknown TSC2 S1130A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1130A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
S1132A missense unknown TSC2 S1132A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1132A results in phosphorylated Tsc2 levels similar to wild-type (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
S1220T missense unknown TSC2 S1220T does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1220T has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S1221L missense unknown TSC2 S1221L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1221L has been identified in sequencing studies (PMID: 29316426), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
S1410L missense no effect - predicted TSC2 S1410L (corresponds to S1433L in the canonical isoform) does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1410L results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
S1420A missense unknown TSC2 S1420A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1420A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
S1431L missense unknown TSC2 S1431L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1431L has been identified in sequencing studies (PMID: 27170661), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S1524L missense unknown TSC2 S1524L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1524L has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S1568C missense unknown TSC2 S1568C lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). S1568C results in inhibition of mTorc1 signaling similar to wild-type Tsc2 in cultured cells, but leads to altered Tsc2 protein folding (PMID: 32502382), and therefore, its effect on Tsc2 protein function is unknown.
S1798A missense loss of function - predicted TSC2 S1798A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1798A results in a loss of phosphorylation by Pim2 and subsequently, prevents Pim2 from relieving suppression of phosphorylated-S6RP compared to wild-type Tsc2 in in vitro assays (PMID: 23818547), and therefore, is predicted to result in a loss of Tsc2 protein function.
S1798F missense unknown TSC2 S1798F does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S1798F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S311F missense unknown TSC2 S311F lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). S311F has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S554L missense unknown TSC2 S554L does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S554L has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
S641R missense unknown TSC2 S641R does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S641R has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S932N missense unknown TSC2 S932N does not lie within any known functional domains of the Tsc2 protein (UniProt.org). S932N has been identified in sequencing studies (PMID: 25233892) but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
S939A missense unknown TSC2 S939A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). The functional effect of S939A is conflicting, as it results in Tsc2 phosphorylation levels, GAP activity towards Rheb, and binding to 14-3-3 and Hamartin similar to wild-type Tsc2 in vitro, however, also demonstrates altered cellular localization, reduced S6k phosphorylation, increased mitotic cell number (PMID: 23818547, PMID: 16636147, PMID: 12582162, PMID: 30629673), diminished binding to 14-3-3 (PMID: 20412061), and loss of phosphorylation and activation of Mtorc1 upon translation inhibition (PMID: 30684133), and therefore, its effect on Tsc2 protein function is unknown.
S981A missense unknown TSC2 S981A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). The functional effect of S981A is conflicting, as it results in Tsc2 phosphorylation levels and GAP activity towards Rheb similar to wild-type, however, also demonstrates altered cellular localization and reduced S6k phosphorylation in culture cells (PMID: 23818547, PMID: 16636147), and therefore, its effect on Tsc2 protein function is unknown.
T1068I missense loss of function TSCS2 T1068I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1068I results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
T1075I missense no effect - predicted TSC2 T1075I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1075I results in inhibition of S6k phosphorylation similar to wild-type Tsc2 in cell culture (PMID: 18854862), and therefore, is predicted to have no effect on Tsc2 protein function.
T1206A missense unknown TSC2 T1206A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1206A has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
T1462A missense no effect - predicted TSC2 T1462A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T1462A results in Tsc2 phosphorylation, binding to 14-3-3, and cellular localization similar to wild-type Tsc2 in culture (PMID: 23818547, PMID: 16636147, PMID: 20412061), and therefore, is predicted to have no effect on Tsc2 protein function.
T147K missense loss of function TSC2 T147K lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). T147K results in disruption of the Tsc complex function as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
T993A missense unknown TSC2 T993A does not lie within any known functional domains of the Tsc2 protein (UniProt.org). T993A results in phosphorylated Tsc2 levels similar to wild-type protein in cell culture (PMID: 23818547), but has not been fully biochemically characterized and therefore, its effect on Tsc2 protein function is unknown.
V1034I missense unknown TSC2 V1034I does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1034I has been identified in sequencing studies (PMID: 27930734), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
V1067E missense loss of function - predicted TSC2 V1067E does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1067E is predicted to confer a loss of function on the Tsc2 protein, as indicated by increased Torc1 activity and decreased Tsc2 expression compared to wild-type Tsc2 in culture (PMID: 29632054).
V1144M missense unknown TSC2 V1144M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V1144M has been identified in the scientific literature (PMID: 22903760), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
V1199G missense loss of function TSC2 V1199G lies within the TSC1-interacting region of the Tsc2 protein (UniProt.org). V1199G results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
V1547I missense loss of function TSC2 V1547I lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1547I results in decreased GAP activity of Tsc2 and increased phosphorylation of S6K in cell culture (PMID: 28215400).
V1623G missense loss of function TSC2 V1623G (corresponding to V1646G in the canonical isoform) lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1623G results in the loss of repression of Mtorc1 as indicated by assays demonstrating increased phosphorylation of S6k in cultured cells (PMID: 18854862).
V1646G missense loss of function TSC2 V1646G lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). R1646G results in destabilization of the Tsc2 protein in an in vitro assay and fails to inhibit mTorc1 signaling in cultured cells (PMID: 32502382), and therefore, results in a loss of Tsc2 protein function.
V1703M missense unknown TSC2 V1703M lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). V1703M has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
V241I missense unknown TSC2 V241I lies within the region required for TSC1 interaction of the Tsc2 protein (UniProt.org). V241I has been identified in the scientific literature (PMID: 32193183), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Apr 2021).
V299fs frameshift loss of function - predicted TSC2 V299fs results in a change in the amino acid sequence of the Tsc2 protein beginning at aa 299 of 766, likely resulting in premature truncation of the functional protein (UniProt.org). V299fs has not been characterized however, due to the effects of other truncation mutations downstream of V299 (PMID: 22903760, PMID: 26703369, PMID: 31454656), is predicted to lead to a loss of Tsc2 protein function.
V461M missense unknown TSC2 V461M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V461M has been identified in sequencing studies (PMID: 28422758, PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
V472M missense unknown TSC2 V472M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V472M has not been characterized in the scientific literature and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
V504D missense loss of function TSC2 V504D does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V504D fails to inhibit Mtorc1 activity as indicated by reduced inhibition of S6k phosphorylation and leads to decreased interaction with Tsc1 in cultured cells (PMID: 31799751).
V550G missense unknown TSC2 V550G does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V550G has been identified in sequencing studies (J Thorac Oncol. Vol 13, Issue 10, S512-S513), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Oct 2021).
V679M missense unknown TSC2 V679M does not lie within any known functional domains of the Tsc2 protein (UniProt.org). V679M has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).
V909Cfs*6 frameshift loss of function - predicted TSC2 V909Cfs*6 indicates a shift in the reading frame starting at amino acid 909 and terminating 6 residues downstream causing a premature truncation of the 1807 amino acid Tsc2 protein (UniProt.org). V909Cfs*6 results in increased phosphorylation of S6k1 and Stat3 in cultured cells (PMID: 31454656), and therefore, is predicted to lead to a loss of Tsc2 protein function.
wild-type none no effect Wild-type TSC2 indicates that no mutation has been detected within the TSC2 gene.
Y1608D missense unknown TSC2 Y1608D lies within the Rap-GAP domain of the Tsc2 protein (UniProt.org). Y1608D has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Tsc2 protein function is unknown (PubMed, Aug 2021).