Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000462774 | SCV000545795 | uncertain significance | Familial adenomatous polyposis 2 | 2018-03-15 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with aspartic acid at codon 104 of the MUTYH protein (p.Tyr104Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 406864). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002323701 | SCV002607994 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-14 | criteria provided, single submitter | clinical testing | The p.Y104D variant (also known as c.310T>G), located in coding exon 3 of the MUTYH gene, results from a T to G substitution at nucleotide position 310. The tyrosine at codon 104 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genetics and Molecular Pathology, |
RCV000462774 | SCV004175363 | uncertain significance | Familial adenomatous polyposis 2 | 2022-08-17 | criteria provided, single submitter | clinical testing |