ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3013C>T (p.Arg1005Ter) (rs63750563)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491215 SCV000580099 pathogenic Hereditary cancer-predisposing syndrome 2017-10-02 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),Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Color RCV000491215 SCV000903435 pathogenic Hereditary cancer-predisposing syndrome 2018-03-22 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000624966 SCV000744294 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2015-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000202164 SCV000279556 pathogenic not provided 2018-06-13 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3013C>T at the cDNA level and p.Arg1005Ter (R1005X) 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 several individuals with Lynch syndrome (Plaschke 2004, Castillejo 2011, Adachi 2017) and is considered pathogenic.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000624966 SCV000743211 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2017-07-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000074795 SCV000695837 pathogenic Lynch syndrome 2015-05-27 criteria provided, single submitter clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074795 SCV000108006 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Invitae RCV000808924 SCV000949057 pathogenic Hereditary nonpolyposis colon cancer 2018-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1005*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs63750563, ExAC 0.002%). This variant has been observed in several individuals affected with colorectal cancer, endometrial cancer and suspected of having Lynch syndrome (PMID: 15483016, 28944238, 27928858, 21247423, 23544471, 26552419). ClinVar contains an entry for this variant (Variation ID: 89330). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202164 SCV000257231 pathogenic not provided no assertion criteria provided research
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202164 SCV000601553 pathogenic not provided 2015-05-08 criteria provided, single submitter clinical testing

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