ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.912dup (p.Ala305fs)

dbSNP: rs863224833
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197610 SCV000255277 pathogenic Lynch syndrome 2015-04-09 criteria provided, single submitter clinical testing This sequence change duplicates 1 nucleotide in exon 5 of the MSH2 mRNA (c.912dupT), causing a frameshift at codon 305. This creates a premature translational stop signal (p.Ala305Cysfs*7) and is expected to result in an absent or disrupted protein product. While this particular sequence change has not been reported in the literature, truncating sequence changes in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000485998 SCV000566843 pathogenic not provided 2019-09-16 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001380946 SCV001579175 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-06-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala305Cysfs*7) 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). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 216863). This variant is not present in population databases (ExAC no frequency).
Myriad Genetics, Inc. RCV003454505 SCV004187032 pathogenic Lynch syndrome 1 2023-07-28 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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