Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012237 | SCV001172664 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-18 | criteria provided, single submitter | clinical testing | The p.M524T variant (also known as c.1571T>C), located in coding exon 16 of the MUTYH gene, results from a T to C substitution at nucleotide position 1571. The methionine at codon 524 is replaced by threonine, an amino acid with similar 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. |
| Invitae | RCV001860698 | SCV002281914 | uncertain significance | Familial adenomatous polyposis 2 | 2021-09-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 819572). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 524 of the MUTYH protein (p.Met524Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. |