ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.263_264del (p.Phe88fs)

dbSNP: rs267607920
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076531 SCV000107546 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001138 SCV001158285 pathogenic not specified 2019-03-13 criteria provided, single submitter clinical testing The MSH2 c.263_264delTT; p.Phe88fs variant (rs267607920) has been described in association with hereditary nonpolyposis colorectal cancer (Bujalkova 2008). It contains an entry in ClinVar (Variation ID: 91029) and is absent from general population databases (Exome Variant Server and Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting 2 nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Bujalkova M et al. Multiplex SNaPshot genotyping for detecting loss of heterozygosity in the mismatch-repair genes MLH1 and MSH2 in microsatellite-unstable tumors. Clin Chem. 2008 Nov;54(11):1844-54.
Invitae RCV001383025 SCV001582033 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-08-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91029). This variant is also known as c.261_262delTT. This premature translational stop signal has been observed in individual(s) with a Lynch syndrome-associated cancer (PMID: 18772310). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe88Cysfs*11) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).
Myriad Genetics, Inc. RCV003452930 SCV004186898 pathogenic Lynch syndrome 1 2023-07-26 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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