ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1229del (p.Gly410fs) (rs1553356700)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657414 SCV000779149 pathogenic not provided 2017-11-16 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH2 is denoted c.1229delG at the cDNA level and p.Gly410ValfsX2 (G410VfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is CAGG[delG]TATA. The deletion causes a frameshift which changes a Glycine to a Valine at codon 410, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH2 c.1229delG has not been reported in the literature as a germline variant, to our knowledge, but has been reported as a somatic variant in a microsatellite unstable (MSI-H) colon cancer (Haraldsdottir 2014). We consider this variant to be pathogenic.
Invitae RCV000685327 SCV000812805 pathogenic Hereditary nonpolyposis colon cancer 2018-08-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly410Valfs*2) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.

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