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Gene Symbol MSH6
Synonyms GTBP | GTMBP | HNPCC5 | HSAP | p160
Gene Description MSH6, mutS homolog 6, binds with Msh2 to form the MutS-alpha complex, which functions in initiation of the DNA mismatch repair system (PMID: 23391514) and is associated with microsatellite instability (MSI) (PMID: 30121009). Mutations in MSH6 are associated with susceptibility to colon cancer and endometrial cancer (PMID: 20028993), and germline MSH6 mutations are associated with Lynch (Hereditary Nonpolyposis Colorectal Cancer) syndrome (PMID: 15528792).
ACMG Incidental List v2.0:
Yes, Lynch syndrome (PMID: 27854360)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A1055P missense loss of function - predicted MSH6 A1055P lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). A1055P demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
A1064T missense unknown MSH6 A1064T lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). A1064T does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
A1204E missense unknown MSH6 A1204E lies within the ATPase domain of the Msh6 protein (PMID: 17531815). A1204E has been identified in sequencing studies (PMID: 22832583), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A1204P missense unknown MSH6 A1204P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). A1204P has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A175T missense unknown MSH6 A175T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A175T has been identified in sequencing studies (PMID: 27302833), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A175V missense unknown MSH6 A175V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A175V demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
A20V missense unknown MSH6 A20V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A20V demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
A25S missense no effect MSH6 A25S does not lie within any known functional domains of the Msh6 protein (UniProt.org). A25S demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 22102614), and was not identified to interfere with Msh6 mismatch repair activity in a functional screen (PMID: 28531214).
A297T missense unknown MSH6 A297T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A297T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A322V missense unknown MSH6 A322V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A322V has been identified in sequencing studies (PMID: 26343386), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A339D missense unknown MSH6 A339D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). A339D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A457D missense unknown MSH6 A457D lies within the mismatch binding region of the Msh6 protein (PMID: 17531815). A457D has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, May 2020).
A457V missense unknown MSH6 A457V lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). A457V has been identified in sequencing studies (PMID: 22622578), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A64V missense unknown MSH6 A64V does not lie within any known functional domains of the Msh6 protein (UniProt.org). A64V has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
A81T missense unknown MSH6 A81T does not lie within any known functional domains of the Msh6 protein (UniProt.org). A81T does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
amp none no effect MSH6 amplification indicates an increased number of copies of the MSH6 gene. However, the mechanism causing the increase is unspecified.
C1165R missense loss of function - predicted MSH6 C1165R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). C1165R (corresponds to C1163R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
C496Y missense unknown MSH6 C496Y lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). C496Y demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
C615F missense unknown MSH6 C615F lies within the connector domain of the Msh6 protein (PMID: 17531815). C615F has been identified in sequencing studies (PMID: 28002797), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
C694R missense loss of function - predicted MSH6 C694R lies within the connector domain of the Msh6 protein (PMID: 17531815). C694R (corresponds to C691R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
C88W missense unknown MSH6 C88W does not lie within any known functional domains of the Msh6 protein (UniProt.org). C88W has been identified in sequencing studies (PMID: 22941188, PMID: 26168399), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D1171fs frameshift loss of function - predicted MSH6 D1171fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1171 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). D1171fs (reported as D1171fs*5) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
D1213E missense loss of function - predicted MSH6 D1213E lies within the ATPase domain of the Msh6 protein (PMID: 17531815). D1213E (corresponds to D1211E in mouse) results in similar ATP and mismatch binding to wild-type protein, but demonstrates reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
D1213G missense loss of function - predicted MSH6 D1213G lies within the ATPase domain of the Msh6 protein (PMID: 17531815). D1213G (corresponds to D1211G in mouse) results in similar ATP and mismatch binding to wild-type protein, but demonstrates reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
D197H missense unknown MSH6 D197H does not lie within any known functional domains of the Msh6 protein (UniProt.org). D197H has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D358E missense unknown MSH6 D358E lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D358E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D358N missense unknown MSH6 D358N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D358N has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D390N missense unknown MSH6 D390N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D390N has been identified in sequencing studies (PMID: 10786688), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D422G missense unknown MSH6 D422G lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D422G has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D530Y missense unknown MSH6 D530Y lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). D530Y has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
D667V missense unknown MSH6 D667V lies within the connector domain of the Msh6 protein (PMID: 17531815). D667V has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Aug 2020).
D803G missense loss of function - predicted MSH6 D803G lies within the lever domain of the Msh6 protein (PMID: 18790734). D803G results in reduced affinity for ATP and decreased Msh6 ATPase activity in in vitro assays (PMID: 18790734), and is therefore predicted to result in a loss of Msh6 protein function.
D89E missense unknown MSH6 D89E does not lie within any known functional domains of the Msh6 protein (UniProt.org). D89E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1163V missense unknown MSH6 E1163V lies within the ATPase domain of the Msh6 protein (PMID: 17531815). E1163V does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
E1196* nonsense unknown MSH6 E1196* results in a premature truncation of the Msh6 protein at amino acid 1196 of 1360 (UniProt.org). E1196* has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1214* nonsense unknown MSH6 E1214* results in a premature truncation of the Msh6 protein at amino acid 1214 of 1360 (UniProt.org). E1214* has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1234* nonsense unknown MSH6 E1234* results in a premature truncation of the Msh6 protein at amino acid 1234 of 1360 (UniProt.org). E1234* has been identified in sequencing studies (PMID: 27149842), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1254del deletion unknown MSH6 E1254del results in the deletion of one amino acid in the ATPase domain of the Msh6 protein at amino acid 1254 (PMID: 17531815). E1254del has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1322* nonsense unknown MSH6 E1322* results in a premature truncation of the Msh6 protein at amino acid 1322 of 1360 (UniProt.org). E1322* has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E1322K missense unknown MSH6 E1322K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). E1322K does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
E171Q missense unknown MSH6 E171Q does not lie within any known functional domains of the Msh6 protein (UniProt.org). E171Q does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
E181A missense unknown MSH6 E181A does not lie within any known functional domains of the Msh6 protein (UniProt.org). E181A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
E220D missense unknown MSH6 E220D does not lie within any known functional domains of the Msh6 protein (UniProt.org). E220D does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
E224* nonsense loss of function - predicted MSH6 E224* results in a premature truncation of the Msh6 protein at amino acid 224 of 1360 (UniProt.org). Due to the loss of most known functional domains (PMID: 17531815), E224* is predicted to lead to a loss of Msh6 protein function.
E286K missense unknown MSH6 E286K does not lie within any known functional domains of the Msh6 protein (UniProt.org). E286K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E463* nonsense loss of function - predicted MSH6 E463* results in a premature truncation of the Msh6 protein at amino acid 463 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E463* is predicted to lead to a loss of Msh6 protein function.
E484K missense unknown MSH6 E484K lies within the mismatch binding region of the Msh6 protein (PMID: 17531815). E484K has been identified in sequencing studies (PMID: 28912153), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, May 2020).
E544D missense unknown MSH6 E544D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). E544D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E544fs frameshift loss of function - predicted MSH6 E544fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 397 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). E544fs (reported as E544fs*26) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
E597Q missense unknown MSH6 E597Q does not lie within any known functional domains of the Msh6 protein (UniProt.org). E597Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E604* nonsense loss of function - predicted MSH6 E604* results in a premature truncation of the Msh6 protein at amino acid 604 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E604* is predicted to lead to a loss of Msh6 protein function.
E619* nonsense loss of function - predicted MSH6 E619* results in a premature truncation of the Msh6 protein at amino acid 619 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E619* is predicted to lead to a loss of Msh6 protein function.
E641* nonsense loss of function - predicted MSH6 E641* results in a premature truncation of the Msh6 protein at amino acid 641 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E641* is predicted to lead to a loss of Msh6 protein function.
E908* nonsense loss of function - predicted MSH6 E908* results in a premature truncation of the Msh6 protein at amino acid 908 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E908* is predicted to lead to a loss of Msh6 protein function.
E946* nonsense loss of function - predicted MSH6 E946* results in a premature truncation of the Msh6 protein at amino acid 946 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), E946* is predicted to lead to a loss of Msh6 protein function.
E956D missense unknown MSH6 E956D does not lie within any known functional domains of the Msh6 protein (UniProt.org). E956D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
E993K missense unknown MSH6 E993K lies within the clamp domain of the Msh6 protein (PMID: 17531815). E993K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
F1088fs frameshift unknown MSH6 F1088fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1088 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). F1088fs has been identified in the scientific literature (PMID: 29571084), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
F1088Lfs*5 frameshift unknown MSH6 F1088Lfs*5 indicates a shift in the reading frame starting at amino acid 1088 and terminating 5 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). F1088Lfs*5 has been identified in sequencing studies (PMID: 30877237, PMID: 29945567, PMID: 28790115), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
F340S missense unknown MSH6 F340S lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). F340S does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
F432L missense loss of function - predicted MSH6 F432L lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). F432L (corresponds to F431L in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
F432S missense loss of function - predicted MSH6 F432S lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). F432S (corresponds to F431S in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
F573fs frameshift loss of function - predicted MSH6 F573fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 573 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss several known functional domains, including the ATPase domain (PMID: 23391514), F573fs is predicted to lead to a loss of Msh6 protein function.
F689L missense unknown MSH6 F689L does not lie within any known functional domains of the Msh6 protein (UniProt.org). F689L has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
F689V missense unknown MSH6 F689V does not lie within any known functional domains of the Msh6 protein (UniProt.org). F689V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
F706S missense loss of function - predicted MSH6 F706S lies within the connector domain of the Msh6 protein (PMID: 17531815). F706S demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G1072C missense unknown MSH6 G1072C does not lie within any known functional domains of the Msh6 protein (UniProt.org). G1072C has been identified in sequencing studies (PMID: 27245685), but has not been biochemically characterized in and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G1139Afs*6 frameshift unknown MSH6 G1139Afs*6 indicates a shift in the reading frame starting at amino acid 1139 and terminating 6 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). G1139Afs*6 has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, May 2020).
G1139D missense loss of function - predicted MSH6 G1139D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1139D (corresponds to G1137D in mouse) results in reduced mismatch binding, impaired ATP binding, and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G1139S missense loss of function MSH6 G1139S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1139S (corresponds to G1137S in mouse) confers a loss of function to the Msh6 protein as demonstrated by reduced mismatch binding and impaired ATP binding (PMID: 31965077), and defective mismatch repair activity in in vitro assays (PMID: 22102614, PMID: 31965077), and elevated microsatellite instability and impaired DNA damage response in mouse cells (PMID: 24040339).
G1157D missense loss of function - predicted MSH6 G1157D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1157D (corresponds to G1155D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G1299C missense unknown MSH6 G1299C lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1299C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G1299D missense unknown MSH6 G1299D lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1299D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G1316R missense unknown MSH6 G1316R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). G1316R has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G141D missense unknown MSH6 G141D lies within the PWWP domain of the Msh6 protein (UniProt.org). G141D has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G289D missense unknown MSH6 G289D does not lie within any known functional domains of the Msh6 protein (UniProt.org). G289D does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
G39E missense unknown MSH6 G39E does not lie within any known functional domains of the Msh6 protein (UniProt.org). G39E is a common Msh6 polymorphism (PMID: 31552911, PMID: 24622885, PMID: 19582761), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G39W missense unknown MSH6 G39W does not lie within any known functional domains of the Msh6 protein (UniProt.org). G39W has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G467D missense unknown MSH6 G467D lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). G467D does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
G520D missense loss of function - predicted MSH6 G520D lies within the connector domain of the Msh6 protein (PMID: 17531815). G520D (corresponds to G519D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G520V missense loss of function - predicted MSH6 G520V lies within the connector domain of the Msh6 protein (PMID: 17531815). G520V (corresponds to G519V in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G529C missense unknown MSH6 G529C lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). G529C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G557D missense loss of function - predicted MSH6 G557D lies within the connector domain of the Msh6 protein (PMID: 17531815). G557D (corresponds to G556D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G566R missense loss of function MSH6 G566R lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). G566R results in deficient ATP binding and decreased Msh6 ATPase activity in in vitro assays (PMID: 18790734).
G624S missense unknown MSH6 G624S lies within the connector domain of the Msh6 protein (PMID: 17531815). G624S has been identified in sequencing studies (PMID: 21097718, PMID: 32095738), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
G686D missense loss of function - predicted MSH6 G686D lies within the connector domain of the Msh6 protein (PMID: 17531815). G686D demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
G93E missense unknown MSH6 G93E lies within the PWWP domain of the Msh6 protein (UniProt.org). G93E has been identified in sequencing studies (PMID: 29245953), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, May 2020).
H1248D missense loss of function MSH6 H1248D lies within the ATPase domain of the Msh6 protein (PMID: 18790734). H1248D results in decreased Msh6 ATPase activity and reduced affinity for mismatch DNA in in vitro assays (PMID: 18790734).
H1248R missense unknown MSH6 H1248R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). H1248R (corresponds to H1246R in mouse) results in similar ATP and mismatch binding to wild-type protein, but demonstrates intermediate mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown.
H367R missense loss of function - predicted MSH6 H367R lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). H367R demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
H437R missense loss of function - predicted MSH6 H437R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). H437R (corresponds to H436R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
H458Y missense loss of function - predicted MSH6 H458Y lies within the mismatch domain of the Msh6 protein (PMID: 17531815). H458Y (corresponds to H457Y in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
I1054F missense unknown MSH6 I1054F lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). I1054F does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
I1109fs frameshift loss of function - predicted MSH6 I1109fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1109 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). I1109fs (reported as I1109fs*3) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
I1113S missense loss of function - predicted MSH6 I1113S lies within the MutS domain 5 of the Msh6 protein (PMID: 23621914). I1113S demonstrates impaired mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
I1183K missense unknown MSH6 I1183K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). I1183K has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I1183T missense unknown MSH6 I1183T lies within the ATPase domain of the Msh6 protein (PMID: 17531815). I1183T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I1357N missense unknown MSH6 I1357N lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). I1357N has been identified in sequencing studies (PMID: 23525077), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I258T missense unknown MSH6 I258T does not lie within any known functional domains of the Msh6 protein (UniProt.org). I258T has been identified in sequencing studies (PMID: 18948947), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I425T missense unknown MSH6 I425T lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). I425T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I516N missense loss of function - predicted MSH6 I516N lies within the mismatch domain of the Msh6 protein (PMID: 17531815). I516N (corresponds to I515N in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
I516Sfs*55 frameshift loss of function - predicted MSH6 I516Sfs*55 indicates a shift in the reading frame starting at amino acid 516 and terminating 55 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). Due to the loss several known functional domains, including the ATPase domain (PMID: 23391514), I516Sfs*55 is predicted to lead to a loss of Msh6 protein function.
I872fs frameshift loss of function - predicted MSH6 I872fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 872 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). (UniProt.org). I872fs (reported as I872fs*10) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
I944V missense unknown MSH6 I944V lies within the clamp domain of the Msh6 protein (PMID: 17531815). I944V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
I967K missense loss of function - predicted MSH6 I967K lies within the clamp domain of the Msh6 protein (PMID: 17531815). I967K (corresponds to I964K in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
inact mut unknown loss of function MSH6 inact mut indicates that this variant results in a loss of function of the Msh6 protein. However, the specific amino acid change has not been identified.
K1009I missense unknown MSH6 K1009I lies within the lever domain of the Msh6 protein (PMID: 17531815). K1009I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K1013N missense unknown MSH6 K1013N lies within the lever domain of the Msh2 protein (PMID: 17531815). K1013N has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K1101N missense unknown MSH6 K1101N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). K1101N is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
K125* nonsense loss of function - predicted MSH6 K125* results in a premature truncation of the Msh6 protein at amino acid 125 of 1360 (UniProt.org). Due to the loss of most known functional domains (PMID: 17531815), K125* is predicted to lead to a loss of Msh6 protein function.
K1358Dfs*2 frameshift unknown MSH6 K1358Dfs*2 indicates a shift in the reading frame starting at amino acid 1358 and terminating 2 residues downstream causing a premature truncation of the 1360 amino acid Msh6 protein (UniProt.org). K1358Dfs*2 has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
K1358fs frameshift unknown MSH6 K1358fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1358 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). K1358fs has been identified in the scientific literature (PMID: 26436112), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K13T missense unknown MSH6 K13T does not lie within any known functional domains of the Msh6 protein (UniProt.org). K13T demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
K155R missense unknown MSH6 K155R does not lie within any known functional domains of the Msh6 protein (UniProt.org). K155R has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020). Y
K185T missense unknown MSH6 K185T does not lie within any known functional domains of the Msh6 protein (UniProt.org). K185T has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K324R missense unknown MSH6 K324R does not lie within any known functional domains of the Msh6 protein (UniProt.org). K324R does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
K417E missense unknown MSH6 K417E lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). K417E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K428T missense unknown MSH6 K428T lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). K428T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K431T missense unknown MSH6 K431T lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). K431T has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Aug 2020).
K646R missense unknown MSH6 K646R lies within the connector domain of the Msh6 protein (PMID: 17531815). K646R has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
K692N missense unknown MSH6 K692N lies within the connector domain of the Msh6 protein (PMID: 17531815). K692N has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
K854M missense unknown MSH6 K854M lies within the lever domain of the Msh6 protein (PMID: 18790734). K854M does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
K885N missense unknown MSH6 K885N lies within the lever domain of the Msh6 protein (PMID: 17531815). K885N has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
K99N missense unknown MSH6 K99N lies within the PWWP domain of the Msh6 protein (UniProt.org). K99N is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
L1063R missense loss of function - predicted MSH6 L1063R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1063R demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L1143P missense loss of function - predicted MSH6 L1143P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1143P (corresponds to L1141P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L1167P missense loss of function - predicted MSH6 L1167P lies within the ATPase domain of the Msh6 protein (PMID: 17531815). L1167P (corresponds to L1165P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L1211P missense loss of function - predicted MSH6 L1211P lies within the Magnesium-binding region of the Msh6 protein (PMID: 12019211). L1211P demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L290* nonsense loss of function - predicted MSH6 L290* results in a premature truncation of the Msh6 protein at amino acid 290 of 1360 (UniProt.org). Due to the loss of most known functional domains (PMID: 23391514), L290* is predicted to lead to a loss of Msh6 protein function.
L373P missense unknown MSH6 L373P lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). L373P has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
L403I missense unknown MSH6 L403I lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). L403I demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
L423I missense unknown MSH6 L423I lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L423I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
L449P missense loss of function - predicted MSH6 L449P lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). L449P (corresponds to L448P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L637P missense loss of function - predicted MSH6 L637P lies within the connector domain of the Msh6 protein (PMID: 17531815). L637P (corresponds to L636P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L681F missense unknown MSH6 L681F within the connector domain of the Msh6 protein (PMID: 17531815). L681F has been identified in sequencing studies (PMID: 22980975, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
L773P missense loss of function - predicted MSH6 L773P lies within the lever domain of the Msh6 protein (PMID: 17531815). L773P (corresponds to L770P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L821P missense loss of function - predicted MSH6 L821P lies within the lever domain of the Msh6 protein (PMID: 17531815). L821P (corresponds to L818P in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
L893Q missense unknown MSH6 L893Q lies within the lever domain of the Msh6 protein (PMID: 17531815). L893Q has been identified in sequencing studies (PMID: 22941188), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
L979V missense unknown MSH6 L979V lies within the clamp domain of the Msh6 protein (PMID: 17531815). L979V has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
loss unknown loss of function MSH6 loss indicates loss of the MSH6 gene, mRNA, and protein.
M1137K missense loss of function - predicted MSH6 M1137K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). M1137K (corresponds to M1135K in mouse) results in impaired ATP binding, decreased mismatch binding, and reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
M1156K missense unknown MSH6 M1156K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). M1156K has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
M452V missense unknown MSH6 M452V lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). M452V has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
M868I missense unknown MSH6 M868I lies within the lever domain of the Msh6 protein (PMID: 17531815). M868I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
M868T missense unknown MSH6 M868T lies within the lever domain of the Msh6 protein (PMID: 17531815). M868T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
mutant unknown unknown MSH6 mutant indicates an unspecified mutation in the MSH6 gene.
N1136K missense loss of function - predicted MSH6 N1136K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). N1136K (corresponds to N1134K in mouse) results in mismatch binding similar to wild-type protein, however, demonstrates deficient ATP binding and mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
N897H missense unknown MSH6 N897H lies within the lever domain of the Msh6 protein (PMID: 17531815). N897H has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
N960T missense unknown MSH6 N960T lies within the clamp domain of the Msh6 protein (PMID: 17531815). N960T has been identified in the scientific literature (PMID: 25224212), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
negative unknown loss of function MSH6 negative indicates a lack of the MSH6 gene, mRNA, and/or protein.
P1073S missense unknown MSH6 P1073S lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). P1073S demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
P1077S missense unknown MSH6 P1077S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1077S has been identified in sequencing studies (PMID: 29245953), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
P1082L missense unknown MSH6 P1082L lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1082L has been identified in sequencing studies (PMID: 25503501), but has not been biochemically chaacterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
P1082S missense unknown MSH6 P1082S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1082S has been identified in the scientific literature (PMID: 24100870), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
P1087R missense no effect MSH6 P1087R lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1087R demonstrates binding to Msh2 and in vitro mismatch repair activity similar to wild-type Msh6 (PMID: 12019211, PMID: 21120944).
P1087T missense no effect MSH6 P1087T lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1087T demonstrates binding to Msh2 and in vitro mismatch repair activity similar to wild-type Msh6 (PMID: 12019211, PMID: 21120944).
P1097S missense unknown MSH6 P1097S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). P1097S has been identified in sequencing studies (PMID: 28002797), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
P233S missense unknown MSH6 P233S does not lie within any known functional domains of the Msh6 protein (UniProt.org). P233S has been identified in sequencing studies (PMID: 22980975), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
P591Q missense unknown MSH6 P591Q lies within the connector domain of the Msh6 protein (PMID: 17531815). P591Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
P768H missense unknown MSH6 P768H lies within the lever domain of the Msh6 protein (PMID: 17531815). P768H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
P781T missense unknown MSH6 P781T lies within the lever domain of the Msh6 protein (PMID: 17531815). P781T has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
positive unknown unknown MSH6 positive indicates the presence of the MSH6 gene, mRNA, and/or protein.
Q485K missense unknown MSH6 Q485K lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). Q485K (corresponds to Q484K in mouse) results in similar ATP binding, intermediate mismatch repair activity, and reduced mismatch binding compared to wild-type protein in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown.
Q485R missense unknown MSH6 Q485R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). Q485R (corresponds to Q484R in mouse) results in similar ATP binding, intermediate mismatch repair activity, and reduced mismatch binding compared to wild-type protein in in vitro assays (PMID: 31965077), and therefore, its effect on Msh6 protein function is unknown.
Q618* nonsense loss of function - predicted MSH6 Q618* results in a premature truncation of the Msh6 protein at amino acid 618 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), Q618* is predicted to lead to a loss of Msh6 protein function.
Q698E missense unknown MSH6 Q698E lies within the connector domain of the Msh6 protein (PMID: 17531815). Q698E has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R1024W missense unknown MSH6 R1024W lies within the lever domain of the Msh6 protein (PMID: 17531815). R1024W is predicted to have a pathogenic effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
R1034Q missense unknown MSH6 R1034Q lies within the lever domain of the Msh6 protein (PMID: 17531815). R1034Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R1076C missense unknown MSH6 R1076C lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1076C has been identified in the scientific literature (PMID: 22250089, PMID: 26832770), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R1076H missense unknown MSH6 R1076H lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1076H has been identified in sequencing studies (PMID: 29263802), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R1095H missense no effect MSH6 R1095H lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1095H demonstrates DNA mismatch repair activity, expression, and MSH2-interaction ability similar to wild-type Msh6 protein in cell culture (PMID: 24040339, PMID: 21120944, PMID: 12522549).
R128H missense unknown MSH6 R128H lies within the PWWP domain of the Msh6 protein (UniProt.org). R128H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Apr 2020).
R1304K missense no effect - predicted MSH6 R1304K lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1304K was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function.
R1331* nonsense unknown MSH6 R1331* results in a premature truncation of the Msh6 protein at amino acid 1331 of 1360 (UniProt.org). R1331* has been identified in the scientific literature (PMID: 26552419, PMID: 16418736), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R1331Q missense unknown MSH6 R1331Q lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1331Q has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, May 2020).
R1334W missense unknown MSH6 R1334W lies within the ATPase domain of the Msh6 protein (PMID: 17531815). R1334W has been identified in sequencing studies (PMID: 25275298), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R178H missense unknown MSH6 R178H does not lie within any known functional domains of the Msh6 protein (UniProt.org). R178H has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R240* nonsense loss of function - predicted MSH6 R240* results in a premature truncation of the Msh6 protein at amino acid 240 of 1360 (UniProt.org). Due to the loss of most known functional domains (PMID: 23391514), R240* is predicted to lead to a loss of Msh6 protein function.
R361H missense unknown MSH6 R361H lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). R361H has been identified in the scientific literature (PMID: 26674132, PMID: 25344691), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R383G missense unknown MSH6 R383G lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). R383G has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R468H missense no effect - predicted MSH6 R468H lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R468H was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function.
R482Q missense unknown MSH6 R482Q lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). R482Q has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
R495* nonsense loss of function - predicted MSH6 R495* results in a premature truncation of the Msh6 protein at amino acid 495 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), R495* is predicted to lead to a loss of Msh6 protein function.
R511G missense loss of function - predicted MSH6 R511G lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). R511G demonstrates deficient mismatch repair activity in a functional screen in mouse cells (PMID: 28531214) and in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
R577H missense unknown MSH6 R577H lies within the connector domain of the Msh6 protein (PMID: 17531815). R577H is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
R644S missense unknown MSH6 R644S lies within the connector domain of the Msh6 protein (PMID: 17531815). R644S is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
R761M missense unknown MSH6 R761M lies within the lever domain of the Msh6 protein (PMID: 17531815). R761M has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R772W missense loss of function MSH6 R772W does not lie within any known functional domains of the Msh6 protein (UniProt.org). R772W confers a loss of function to the Msh6 protein as demonstrated by impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087).
R791C missense unknown MSH6 R791C lies within the lever domain of the Msh6 protein (PMID: 17531815). R791C has been identified in sequencing studies (PMID: 25855536), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R791H missense unknown MSH6 R791H lies within the lever domain of the Msh6 protein (PMID: 17531815). R791H has been identified in sequencing studies (PMID: 25233892), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R922* nonsense loss of function - predicted MSH6 R922* results in a premature truncation of the Msh6 protein at amino acid 922 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), R922* is predicted to lead to a loss of Msh6 protein function.
R922Q missense no effect - predicted MSH6 R922Q lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). R922Q was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function.
R959H missense unknown MSH6 R959H lies within the clamp domain of the Msh6 protein (PMID: 17531815). R959H has been identified in sequencing studies (PMID: 26648449, PMID: 29596542), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R961I missense unknown MSH6 R961I lies within the clamp domain of the Msh6 protein (PMID: 17531815). R961I has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
R976H missense unknown MSH6 R976H lies within the clamp domain of the Msh6 protein (PMID: 18790734). R976H results in decreased Msh6 affinity for ADP and mismatched DNA in cell culture (PMID: 18790734), however, in another study demonstrated proficient mismatch repair activity (PMID: 22102614), and therefore, its effect on Msh6 protein function is unknown.
S1028L missense unknown MSH6 S1028L lies within the lever domain of the Msh6 protein (PMID: 17531815). S1028L has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S1049F missense unknown MSH6 S1049F lies within the lever domain of the Msh6 protein (PMID: 17531815). S1049F is predicted to have a moderate effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S1067I missense unknown MSH6 S1067I lies within the lever domain of the Msh6 protein (PMID: 17531815). S1067I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S1188N missense loss of function - predicted MSH6 S1188N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1188N demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
S1208F missense unknown MSH6 S1208F lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1208F has been identified in sequencing studies (PMID: 24628946), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S1279N missense unknown MSH6 S1279N lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1279N has been identified in sequencing studies (PMID: 30171174), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S1329L missense unknown MSH6 S1329L lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1329L does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S1340G missense unknown MSH6 S1340G lies within the ATPase domain of the Msh6 protein (PMID: 17531815). S1340G does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S144I missense no effect MSH6 S144I lies within the PWWP domain of the Msh6 protein (UniProt.org). S144I demonstrates proficient mismatch repair activity in an in vitro assay (PMID: 31965077), and similar Msh2 and DNA binding to wild-type Msh6 in cultured cells (PMID: 12019211, PMID: 18484749, PMID: 21120944).
S285I missense no effect - predicted MSH6 S285I lies within the mismatch binding domain of the Msh6 protein (PMID: 18790734). S285I demonstrates mismatch stimulated ATPase activity similar to wild-type Msh6 protein in an in vitro ATPase assay (PMID: 18790734), and is therefore predicted to have no effect on Msh6 protein function.
S314I missense unknown MSH6 S314I does not lie within any known functional domains of the Msh6 protein (UniProt.org). S314I is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S321* nonsense loss of function - predicted MSH6 S321* results in a premature truncation of the Msh6 protein at amino acid 321 of 1360 (UniProt.org). Due to the loss of most known functional domains (PMID: 23391514), S321* is predicted to lead to a loss of Msh6 protein function.
S341A missense unknown MSH6 S341A lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). S341A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S360I missense unknown MSH6 S360I lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). S360I is predicted to have no effect on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
S394A missense unknown MSH6 S394A lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). S394A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S503C missense unknown MSH6 S503C does not lie within any known functional domains of the Msh6 protein (UniProt.org). S503C demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S580L missense loss of function - predicted MSH6 S580L lies within the MutS domain 2 of the Msh6 protein (PMID: 23621914). S580L demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
S65L missense unknown MSH6 S65L does not lie within any known functional domains of the Msh6 protein (UniProt.org). S65L demonstrates intermediate mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
S668C missense unknown MSH6 S668C lies within the connector domain of the Msh6 protein (PMID: 17531815). S668C has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S677I missense unknown MSH6 S677I lies within the connector domain of the Msh6 protein (PMID: 17531815). S677I has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
S702* nonsense loss of function - predicted MSH6 S702* results in a premature truncation of the Msh6 protein at amino acid 1044 of 1360 (UniProt.org). S702* has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
S884T missense loss of function - predicted MSH6 S884T lies within the lever domain of the Msh6 protein (PMID: 17531815). S884T (corresponds to S881T in mouse) results in similar ATP binding to wild-type protein, but demonstrates decreased mismatch binding and reduced mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
S950I missense unknown MSH6 S950I lies within the clamp domain of the Msh6 protein (PMID: 17531815). S950I has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1008I missense loss of function - predicted MSH6 T1008I lies within the clamp domain of the Msh6 protein (PMID: 17531815). T1008I (corresponds to T1005I in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
T1010A missense unknown MSH6 T1010A lies within the lever domain of the Msh6 protein (PMID: 17531815). T1010A has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1085fs frameshift unknown MSH6 T1085fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 1085 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). T1085fs has been identified in sequencing studies (PMID: 23417712), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jul 2020).
T1189I missense unknown MSH6 T1189I lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1189I has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1205I missense unknown MSH6 T1205I lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1205I has been identified in sequencing studies (PMID: 28002797), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1219I missense loss of function MSH6 T1219I does not lie within any known functional domains of the Msh6 protein (UniProt.org). T1219I results in a loss of Msh6 protein function, as indicated by loss of mismatch-induced conformational changes and defective DNA mismatch repair activity in in vitro assays (PMID: 22277660, PMID: 31965077).
T1225M missense unknown MSH6 T1225M lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1225M demonstrates proficient mismatch repair activity compared to wild-type protein in in vitro assays (PMID: 22102614, PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
T1238A missense unknown MSH6 T1238A lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1238A has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1247S missense unknown MSH6 T1247S lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1247S has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T1284M missense unknown MSH6 T1284M lies within the ATPase domain of the Msh6 protein (PMID: 17531815). T1284M does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
T269S missense unknown MSH6 T269S does not lie within any known functional domains of the Msh6 protein (UniProt.org). T269S is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T521K missense loss of function - predicted MSH6 T521K lies within the connector domain of the Msh6 protein (PMID: 17531815). T521K (corresponds to T520K in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
T750P missense unknown MSH6 T750P lies within the lever domain of the Msh6 protein (PMID: 17531815). T750P has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T757I missense unknown MSH6 T757I lies within the lever domain of the Msh6 protein (PMID: 17531815). T757I has been identified in sequencing studies (PMID: 25078279, PMID: 22622578, PMID: 31471491), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
T767I missense loss of function - predicted MSH6 T767I lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). T767I demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V1056M missense unknown MSH6 V1056M lies within the lever domain of the Msh6 protein (PMID: 17531815). V1056M is predicted to have no impact on Msh6 protein function by computational analysis (PMID: 23621914), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
V1350A missense unknown MSH6 V1350A lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). V1350A has been identified in sequencing studies (PMID: 22037554), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
V304A missense unknown MSH6 V304A does not lie within any known functional domains of the Msh6 protein (UniProt.org). V304A does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
V398E missense loss of function - predicted MSH6 V398E lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). V398E demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V424G missense loss of function - predicted MSH6 V424G lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V424G (corresponds to V423G in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V450A missense unknown MSH6 V450A lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). V450A has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
V480E missense loss of function - predicted MSH6 V480E lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). V480E demonstrates deficient mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V480L missense unknown MSH6 V480L lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). V480L has been identified in the scientific literature (PMID: 12732731), but has not been biochemically characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
V508E missense loss of function - predicted MSH6 V508E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V508E (corresponds to V507E in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V509A missense no effect - predicted MSH6 V509A lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V509A was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function.
V509E missense loss of function - predicted MSH6 V509E lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). V509E (corresponds to V508E in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V688D missense loss of function - predicted MSH6 V688D lies within the connector domain of the Msh6 protein (PMID: 17531815). V688D (corresponds to V685D in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
V800L missense unknown MSH6 V800L lies within the lever domain of the Msh6 protein (PMID: 17531815). V800L does not demonstrate reduced mismatch repair activity compared to wild-type protein in an in vitro assay (PMID: 31965077), but has not been fully biochemically characterized and therefore, its effect on Msh6 protein function is unknown.
V878A missense unknown MSH6 V878A lies within the MutS domain 3 of the Msh6 protein (PMID: 23621914). The functional effect of V878A is conflicting, as it demonstrates decreased Msh6 ATPase activity in vitro in one study (PMID: 18790734), but demonstrates proficient mismatch repair activity in an in vitro assay in another study (PMID: 22102614), and therefore, its effect on Msh6 protein function is unknown (PubMed, Aug 2020).
W1047* nonsense loss of function - predicted MSH6 W1047* results in a premature truncation of the Msh6 protein at amino acid 1047 of 1360 (UniProt.org). Due to the loss the ATPase domain (PMID: 23391514), W1047* is predicted to lead to a loss of Msh6 protein function.
W142* nonsense loss of function - predicted MSH6 W142* results in a premature truncation of the Msh6 protein at amino acid 1044 of 1360 (UniProt.org). W142* has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
W372R missense loss of function - predicted MSH6 W372R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). W372R (corresponds to W371R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
W413R missense loss of function - predicted MSH6 W413R lies within the mismatch binding domain of the Msh6 protein (PMID: 17531815). W413R (corresponds to W412R in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
W628* nonsense loss of function - predicted MSH6 W628* results in a premature truncation of the Msh6 protein at amino acid 628 of 1360 (UniProt.org). Due to the loss of several known functional domains, including the ATPase domain (PMID: 23391514), W628* is predicted to lead to a loss of Msh6 protein function.
W777* nonsense loss of function - predicted MSH6 W777* results in a premature truncation of the Msh6 protein at amino acid 777 of 1360 (UniProt.org). Due to the several known functional domains, including the ATPase domain (PMID: 23391514), W777* is predicted to lead to a loss of Msh6 protein function.
W912R missense unknown MSH6 W912R lies within the lever domain of the Msh6 protein (PMID: 17531815). W912R has not been characterized and therefore, its effect on Msh6 protein function is unknown (PubMed, Jun 2020).
Y1006N missense loss of function - predicted MSH6 Y1006N lies within the clamp domain of the Msh6 protein (PMID: 17531815). Y1006N (corresponds to Y1003N in mouse) results in impaired mismatch binding and deficient mismatch repair activity in in vitro assays (PMID: 31965077), and therefore, is predicted to lead to a loss of Msh6 protein function.
Y1044* nonsense loss of function - predicted MSH6 Y1044* results in a premature truncation of the Msh6 protein at amino acid 1044 of 1360 (UniProt.org). Due to the loss of the ATPase domain (PMID: 23391514), Y1044* is predicted to lead to a loss of Msh6 protein function.
Y397fs frameshift loss of function - predicted MSH6 Y397fs results in a change in the amino acid sequence of the Msh6 protein beginning at aa 397 of 1360, likely resulting in premature truncation of the functional protein (UniProt.org). Y397fs (reported as Y397fs*3) has not been biochemically characterized, but is associated with a loss of Msh6 protein expression and increased microsatellite instability in tumor samples (PMID: 14974087), and is therefore predicted to result in a loss of Msh6 protein function.
Y397H missense unknown MSH6 Y397H lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). Y397H has not been characterized in the scientific literature and therefore, its effect on Msh6 protein function is unknown (PubMed, Sep 2020).
Y556F missense no effect - predicted MSH6 Y556F lies within an MSH2-binding region of the Msh6 protein (PMID: 12019211). Y556F was not identified to interfere with Msh6 mismatch repair activity in a functional screen in mouse cells (PMID: 28531214), and did not demonstrate mismatch repair deficiency in an in vitro assay (PMID: 31965077), and therefore, is predicted to have no effect on Msh6 protein function.