Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129217 | SCV000183968 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-18 | criteria provided, single submitter | clinical testing | The p.V496M variant (also known as c.1486G>A), located in coding exon 15 of the MUTYH gene, results from a G to A substitution at nucleotide position 1486. The valine at codon 496 is replaced by methionine, 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. |
Labcorp Genetics |
RCV000226351 | SCV000285934 | uncertain significance | Familial adenomatous polyposis 2 | 2022-09-10 | criteria provided, single submitter | clinical testing | 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. 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 methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 140942). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 496 of the MUTYH protein (p.Val496Met). |
Counsyl | RCV000226351 | SCV000487318 | uncertain significance | Familial adenomatous polyposis 2 | 2015-12-13 | criteria provided, single submitter | clinical testing |