ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3083C>G (p.Ser1028Ter) (rs876660853)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491967 SCV000580098 pathogenic Hereditary cancer-predisposing syndrome 2016-11-22 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)
GeneDx RCV000481140 SCV000571052 pathogenic not provided 2016-07-25 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3083C>G at the cDNA level and p.Ser1028Ter (S1028X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual with endometrial cancer (Le Gallo 2012) and is considered pathogenic.
Invitae RCV000794243 SCV000933637 pathogenic Hereditary nonpolyposis colon cancer 2018-11-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1028*) 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 affected with endometrial cancer (PMID: 23104009). ClinVar contains an entry for this variant (Variation ID: 421754). 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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