ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.643G>A (p.Val215Met) (rs776487884)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164298 SCV000214928 likely pathogenic Hereditary cancer-predisposing syndrome 2020-09-18 criteria provided, single submitter clinical testing The p.V215M variant (also known as c.643G>A), located in coding exon 8 of the MUTYH gene, results from a G to A substitution at nucleotide position 643. The valine at codon 215 is replaced by methionine, an amino acid with highly similar properties. This variant has been detected in both a homozyous state and in conjunction with a likely pathogenic variant in MUTYH by our laboratory in patients with polyposis. This alteration has also been reported in conjunction with a MUTYH pathogenic variant in an individual diagnosed at age 30 with colorectal cancer as well as numerous colorectal and duodenal adenomas and has a high probability of being in trans given it has co-occurred with multiple different mutations (Nielsen M et al. Gastroenterology. 2009 Feb;136:471-6; Jones N et al. Gastroenterology. 2009 Aug;137:489-94, 494.e1; quiz 725-6; Vogt S. Gastroenterology. 2009 Dec;137(6):1976-85.e1-10). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000502295 SCV000639349 uncertain significance MYH-associated polyposis 2020-10-25 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 215 of the MUTYH protein (p.Val215Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs776487884, ExAC 0.04%). This variant has been observed in individuals affected with adenomatous polyposis (PMID: 19732775, 20618354, 19032956). ClinVar contains an entry for this variant (Variation ID: 184952). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 5
Color Health, Inc RCV000164298 SCV000690595 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358407 SCV001554131 pathogenic not provided no assertion criteria provided clinical testing

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