Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001009989 | SCV001170126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | The p.K38R variant (also known as c.113A>G), located in coding exon 2 of the MUTYH gene, results from an A to G substitution at nucleotide position 113. The lysine at codon 38 is replaced by arginine, 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. |
Invitae | RCV001212919 | SCV001384529 | uncertain significance | Familial adenomatous polyposis 2 | 2020-03-02 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 38 of the MUTYH protein (p.Lys38Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. 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 arginine 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. This variant has not been reported in the literature in individuals with MUTYH-related conditions. This variant is not present in population databases (ExAC no frequency). |