Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237521 | SCV001410284 | uncertain significance | Familial adenomatous polyposis 2 | 2023-07-25 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects MUTYH function (PMID: 25820570). 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 963489). This missense change has been observed in individual(s) with colorectal adenomas or colorectal cancer (PMID: 14991577, 17949294). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 459 of the MUTYH protein (p.Ala459Thr). 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. |