ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.3414dup (p.Cys1139fs) (rs267608118)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074937 SCV000108151 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000214022 SCV000275659 pathogenic Hereditary cancer-predisposing syndrome 2018-08-24 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000214836 SCV000279615 pathogenic not provided 2016-10-14 criteria provided, single submitter clinical testing This duplication of one nucleotide in MSH6 is denoted c.3804dupA at the cDNA level and p.Cys1269MetfsX6 (C1269MfsX6) at the protein level. The normal sequence, with the base that is duplicated in braces, is agGC[A]TGCA, where the capital letters are exonic and the lower case are intronic. The duplication causes a frameshift which changes a Cysteine to a Methionine at codon 1269, and creates a premature stop codon at position 6 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH6 c.3804dupA has been identified in individuals with Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (Stormorken 2005, Sjursen 2010). We consider this variant to be pathogenic.
Invitae RCV000684821 SCV000551241 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-12-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys1269Metfs*6) 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 reported in the literature in multiple families and individuals affected with Lynch syndrome (PMID: 20587412, 26483394). ClinVar contains an entry for this variant (Variation ID: 89469). 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 RCV000214022 SCV000905459 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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