ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1691C>A (p.Ser564Ter) (rs864622153)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491176 SCV000580348 pathogenic Hereditary cancer-predisposing syndrome 2017-05-30 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 RCV000491176 SCV000690217 pathogenic Hereditary cancer-predisposing syndrome 2017-09-15 criteria provided, single submitter clinical testing
Counsyl RCV000576302 SCV000677830 likely pathogenic Hereditary nonpolyposis colorectal cancer type 5 2016-12-12 criteria provided, single submitter clinical testing
GeneDx RCV000481005 SCV000570637 pathogenic not provided 2017-04-14 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.1691C>A at the cDNA level and p.Ser564Ter (S564X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been observed in an individual tested on a hereditary colorectal cancer panel (Ferber 2016). We consider this variant to be pathogenic.
Invitae RCV000204908 SCV000259478 pathogenic Hereditary nonpolyposis colon cancer 2018-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 564 (p.Ser564*) of the MSH6 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). A different variant (c.1691C>G), giving rise to the same protein effect observed here (p.Ser564*), has been reported in 2 families with Lynch syndrome (PMID: 27601186). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000481005 SCV000888247 pathogenic not provided 2018-01-16 criteria provided, single submitter clinical testing

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