ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.1495G>T (p.Val499Leu) (rs780209880)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233321 SCV000285936 uncertain significance MYH-associated polyposis 2020-07-08 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 513 of the MUTYH protein (p.Val513Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs780209880, ExAC 0.001%). This variant has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 238340). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on MUTYH function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000572039 SCV000662644 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing The p.V513L variant (also known as c.1537G>T), located in coding exon 16 of the MUTYH gene, results from a G to T substitution at nucleotide position 1537. The valine at codon 513 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl RCV000233321 SCV000797073 uncertain significance MYH-associated polyposis 2018-01-10 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000993995 SCV001147264 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000572039 SCV001350591 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-08 criteria provided, single submitter clinical testing This missense variant replaces valine with leucine at codon 513 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251418 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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