ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.2718_2719del (p.Phe907fs) (rs1553414519)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630021 SCV000750977 pathogenic Hereditary nonpolyposis colon cancer 2019-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe1037Leufs*2) 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 an individual affected with Lynch syndrome (PMID: 27064304). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000781601 SCV000919773 likely pathogenic Lynch syndrome 2018-11-06 criteria provided, single submitter clinical testing Variant summary: MSH6 c.3108_3109delGT (p.Phe1037LeufsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Glu1052fsX13 and p.Arg1068X). The variant was absent in 244248 control chromosomes (gnomAD). The variant, c.3108_3109delGT, has been reported in the literature in individuals affected with Lynch Syndrome (Sjursen_2015, DeRycke_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and both classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Ambry Genetics RCV001018672 SCV001179937 pathogenic Hereditary cancer-predisposing syndrome 2018-02-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV001018672 SCV001352405 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000656573 SCV000778621 likely pathogenic not provided 2018-02-12 no assertion criteria provided clinical testing

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