ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.1352del (p.Phe451fs) (rs869312769)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000490853 SCV000580124 pathogenic Hereditary cancer-predisposing syndrome 2017-08-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000480743 SCV000571367 pathogenic not provided 2018-07-31 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH6 is denoted c.1352delT at the cDNA level and p.Phe451SerfsX2 (F451SfsX2) at the protein level. The normal sequence, with the base that is deleted in braces, is GTAT[T]CATG. The deletion causes a frameshift which changes a Phenylalanine to a Serine at codon 451, and creates a premature stop codon at position 2 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000684808 SCV000551304 pathogenic Hereditary nonpolyposis colon cancer 2018-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe451Serfs*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 the literature in an individual affected with small intestine cancer and polyposis (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 224534). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000480743 SCV000691926 likely pathogenic not provided no assertion criteria provided clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000210100 SCV000266089 pathogenic Lynch syndrome 2015-11-20 criteria provided, single submitter clinical testing

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