Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001017754 | SCV001178886 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-17 | criteria provided, single submitter | clinical testing | The p.S99R variant (also known as c.297C>A), located in coding exon 3 of the MUTYH gene, results from a C to A substitution at nucleotide position 297. The serine at codon 99 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly 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. |
Color Diagnostics, |
RCV001017754 | SCV001345767 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-22 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with arginine at codon 99 of the MUTYH protein. Computational prediction tool 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 performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |
Invitae | RCV001228835 | SCV001401255 | uncertain significance | Familial adenomatous polyposis 2 | 2023-02-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 99 of the MUTYH protein (p.Ser99Arg). This variant is not present in population databases (gnomAD no frequency). 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: 822410). 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 arginine 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. |
Mendelics | RCV002249633 | SCV002518329 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing |