ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1969del (p.Gln657fs) (rs876661205)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491140 SCV000580105 pathogenic Hereditary cancer-predisposing syndrome 2017-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000491140 SCV000685242 pathogenic Hereditary cancer-predisposing syndrome 2017-03-28 criteria provided, single submitter clinical testing
GeneDx RCV000215322 SCV000279781 pathogenic not provided 2018-07-27 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.1969delC at the cDNA level and p.Gln657ArgfsX6 (Q657RfsX6) at the protein level. The normal sequence, with the base that is deleted in braces, is ACCC[C]AGGT. The deletion causes a frameshift, which changes a Glutamine to an Arginine at codon 657, and creates a premature stop codon at position 6 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. MSH6 c.1969delC has been observed in a woman with endometrial cancer (Goodfellow 2015). We consider this variant to be pathogenic.
Invitae RCV000557139 SCV000624705 pathogenic Hereditary nonpolyposis colon cancer 2018-08-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln657Argfs*6) in the MSH6 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 with endometrial cancer (PMID: 26552419). ClinVar contains an entry for this variant (Variation ID: 234761). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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