ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.742C>T (p.Arg248Ter) (rs63749980)

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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 RCV000490932 SCV000580084 pathogenic Hereditary cancer-predisposing syndrome 2017-06-05 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 RCV000486750 SCV000566643 pathogenic not provided 2018-11-05 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.742C>T at the cDNA level and p.Arg248Ter (R248X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>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 two families with Lynch syndrome (Wijnen 1999, Hendriks 2003, Steinke 2008) and is considered pathogenic.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075032 SCV000108253 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000524215 SCV000253781 pathogenic Hereditary nonpolyposis colon cancer 2018-07-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 248 (p.Arg248*) of the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with Lynch syndrome (PMID: 10508506, 18301448). For these reasons, this variant has been classified as Pathogenic.

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