ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.997T>C (p.Cys333Arg) (rs63750468)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000076777 SCV000259666 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-08-27 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 333 of the MSH2 protein (p.Cys333Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual and families with Lynch syndrome related cancers (PMID: 11379475, Invitae). ClinVar contains an entry for this variant (Variation ID: 91272). This variant has been reported to affect MSH2 protein function (PMID: 20176959, 17720936). This variant disrupts the p.Cys333 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16175654, 17101317, 21642682, 18951462, 26951660). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491354 SCV000580566 likely pathogenic Hereditary cancer-predisposing syndrome 2016-04-29 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Insufficient or conflicting evidence

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