ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2910G>A (p.Trp970Ter) (rs765411990)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491637 SCV000580332 pathogenic Hereditary cancer-predisposing syndrome 2020-01-08 criteria provided, single submitter clinical testing The p.W970* pathogenic mutation (also known as c.2910G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 2910. This changes the amino acid from a tryptophan to a stop codon within coding exon 4. This mutation was identified in a cohort of 4439 women with ovarian cancer who underwent multi gene panel testing for hereditary cancer (Carter NJ et al. Gynecol. Oncol. 2018 12;151:481-488). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
GeneDx RCV000657724 SCV000779474 pathogenic not provided 2017-06-08 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.2910G>A at the cDNA level and p.Trp970Ter (W970X) at the protein level. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has not, to our knowledge, been published in the literature as a germline variant; however, it has been reported as a somatic variant in an epithelial ovarian tumor (Jean 2016). We consider this variant to be pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000657724 SCV000592617 uncertain significance not provided no assertion criteria provided clinical testing

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