ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.876dup (p.Thr293fs) (rs1553352505)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478647 SCV000570725 pathogenic not provided 2016-09-27 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH2 is denoted c.876dupT at the cDNA level and p.Thr293TyrfsX3 (T293YfsX3) at the protein level. The normal sequence, with the base that is duplicated in braces, is TGAC[T]ACTT. The duplication causes a frameshift which changes a Threonine to a Tyrosine at codon 293, and creates a premature stop codon at position 3 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000800562 SCV000940286 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-01-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr293Tyrfs*3) 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. ClinVar contains an entry for this variant (Variation ID: 421500). 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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