ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.186_187dup (p.Val63fs)

dbSNP: rs63750160
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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) RCV000076308 SCV000107326 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000491030 SCV000580408 pathogenic Hereditary cancer-predisposing syndrome 2023-01-18 criteria provided, single submitter clinical testing The c.186_187dupGG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a duplication of GG at nucleotide positions 186 to 187, causing a translational frameshift with a predicted alternate stop codon (p.V63Gfs*2). This mutation has been reported in an individual who was diagnosed with colorectal cancer at age 51 as well as endometrial cancer (Talseth-Palmer BA et al. Cancer Med, 2016 May;5:929-41). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001854319 SCV002218418 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-04-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Lynch syndrome (PMID: 26811195). ClinVar contains an entry for this variant (Variation ID: 90806). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val63Glyfs*2) 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. RCV003452864 SCV004186997 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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