ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.2878_2884del (p.Glu960fs) (rs587779259)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074833 SCV000108044 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000483834 SCV000567781 pathogenic not provided 2015-08-28 criteria provided, single submitter clinical testing This deletion of 7 nucleotides in MSH6 is denoted c.3268_3274delGAGCTTA at the cDNA level and p.Glu1090LysfsX23 (E1090KfsX23) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTTA[GAGCTTA]AAGG. The deletion causes a frameshift, which changes a Glutamic Acid to a Lysine at codon 1090, and creates a premature stop codon at position 23 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.3268_3274delGAGCTTA, also reported as c.3264_3270del, has been observed in at least one individual with Lynch syndrome (Canard 2012). we consider this variant to be pathogenic.
Ambry Genetics RCV000573738 SCV000670037 pathogenic Hereditary cancer-predisposing syndrome 2017-01-26 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000629992 SCV000750948 pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-11-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1090Lysfs*23) 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 individuals affected with Lynch syndrome (PMID: 20487569, 27601186). This variant has been reported in individuals in the Universal Mutation Database (PMID: 23729658). ClinVar contains an entry for this variant (Variation ID: 89366). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.

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