ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.3457_3460dup (p.Thr1154fs) (rs267608128)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074943 SCV000108157 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000214756 SCV000273206 pathogenic Hereditary cancer-predisposing syndrome 2019-01-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000524190 SCV000551186 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-11-20 criteria provided, single submitter clinical testing This sequence change inserts 4 nucleotides in exon 9 of the MSH6 mRNA (c.3847_3850dupATTA), causing a frameshift at codon 1284. This creates a premature translational stop signal (p.Thr1284Asnfs*6) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic. This particular variant has been reported in families affected with Lynch syndrome (PMID: 22495361). It is also called c.3850_3851insATTA in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000484754 SCV000568729 pathogenic not provided 2017-11-13 criteria provided, single submitter clinical testing This duplication of 4 nucleotides in MSH6 is denoted c.3847_3850dupATTA at the cDNA level and p.Thr1284AsnfsX6 (T1284NfsX6) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GACT[ATTA]CGTT. The duplication causes a frameshift which changes a Threonine to an Asparagine at codon 1284, 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.3847_3850dupATTA has been associated with Lynch Syndrome (Nilbert 2009, Klarskov 2011, Okkels 2012). We consider this variant to be pathogenic.
Counsyl RCV000576567 SCV000677791 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2016-12-28 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000576567 SCV000993567 pathogenic Hereditary nonpolyposis colorectal cancer type 5 2018-09-11 criteria provided, single submitter research

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