ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2061T>A (p.Cys687Ter) (rs267608068)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074710 SCV000107917 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000162397 SCV000212720 pathogenic Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Other acmg-defined mutation (i.e. initiation codon or gross deletion);Other data supporting pathogenic classification
GeneDx RCV000201965 SCV000490620 pathogenic not provided 2017-10-26 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH6 c.2061T>A at the cDNA level and p.Cys687Ter (C687X) atthe protein level. The substitution creates a nonsense variant, which changes a Cysteine to a premature stop codon(TGT>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 an individual with a tubular adenoma and in a Scottish familywith multiple cases of colorectal or Lynch syndrome cancers (Pino 2009, Baglietto 2010), and is consideredpathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000074710 SCV000592595 pathogenic Lynch syndrome 2015-08-11 criteria provided, single submitter clinical testing
Invitae RCV000530716 SCV000624721 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-10-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys687*) 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 Lynch syndrome (PMID: 19324997). ClinVar contains an entry for this variant (Variation ID: 89246). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Color RCV000162397 SCV000685252 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000201965 SCV000257218 likely pathogenic not provided no assertion criteria provided clinical testing

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