ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.11dup (p.Pro5fs) (rs730881775)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160630 SCV000211229 pathogenic not provided 2016-08-09 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH2 is denoted c.11dupA at the cDNA level and p.Pro5AlafsX77 (P5AfsX77) at the protein level. The normal sequence, with the base that is duplicated in braces, is GTGC[A]GCCG. The duplication causes a frameshift, which changes a Proline to an Alanine at codon 5, and creates a premature stop codon at position 77 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.11dupA has been observed in at least one individual with colon cancer (Susswein 2015). We consider this variant to be pathogenic.
Ambry Genetics RCV000491987 SCV000580496 pathogenic Hereditary cancer-predisposing syndrome 2019-01-17 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160630 SCV001134328 pathogenic not provided 2018-11-02 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Invitae RCV001204547 SCV001375758 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-09-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro5Alafs*77) 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 been observed in an individual affected with colon cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182592). 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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