Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000233321 | SCV000285936 | uncertain significance | Familial adenomatous polyposis 2 | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 513 of the MUTYH protein (p.Val513Leu). This variant is present in population databases (rs780209880, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV000572039 | SCV000662644 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-18 | 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. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 2/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). 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 | Familial adenomatous polyposis 2 | 2018-01-10 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000572039 | SCV001350591 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-28 | 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. |
| Sema4, |
RCV000572039 | SCV002532251 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-06 | criteria provided, single submitter | curation |