ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.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) RCV000076311 SCV000107332 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000570107 SCV000669859 pathogenic Hereditary cancer-predisposing syndrome 2023-09-22 criteria provided, single submitter clinical testing The c.187dupG pathogenic mutation, located in coding exon 1 of the MSH2 gene, results from a duplication of G at nucleotide position 187, causing a translational frameshift with a predicted alternate stop codon (p.V63Gfs*19). This mutation, designated as "G5>G6 frameshift at 183-187," was identified in a Taiwanese HNPCC family meeting Amsterdam II criteria (Huang RL et al. Cancer Genet. Cytogenet. 2004 Sep;153:108-14). 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.
Myriad Genetics, Inc. RCV003452866 SCV004187926 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.
Invitae RCV003593897 SCV004292473 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-06-20 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: 90809). This variant is also known as G5 to G6 frame-shift at 183–187. This premature translational stop signal has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 11393127, 31615790). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val63Glyfs*19) 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).

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