Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237613 | SCV001410379 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-07-14 | criteria provided, single submitter | clinical testing | 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. 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. This variant disrupts the p.Ser685 amino acid residue in MLH1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32076465). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 685 of the MLH1 protein (p.Ser685Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. |