ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.1244_1247del (p.Lys415fs) (rs63749874)

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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) RCV000074674 SCV000107877 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000497289 SCV000149287 pathogenic not provided 2018-08-28 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH6 c.1634_1637delAAGA at the cDNA level and p.Lys545ArgfsX25 (K545RfsX25) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GAAA[delAAGA]GGAA. The deletion causes a frameshift, which changes a Lysine to an Arginine at codon 545, and creates a premature stop codon at position 25 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.1634_1637delAAGA has been reported in individuals with Lynch syndrome (Arnold 2007, Kidambi 2017), and is considered to be pathogenic.
Ambry Genetics RCV000115378 SCV000214467 pathogenic Hereditary cancer-predisposing syndrome 2018-03-02 criteria provided, single submitter clinical testing 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
Invitae RCV000630020 SCV000750976 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys545Argfs*25) 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 individuals affected with Lynch syndrome, as well as in individuals with clinical features of Lynch syndrome (PMID: 17323113, 28283864, 28514183). ClinVar contains an entry for this variant (Variation ID: 89211). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000761604 SCV000891769 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2018-08-24 criteria provided, single submitter research ACMG codes: PVS1, PM2, PP5

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