Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001321023 | SCV001511836 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2020-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with alanine at codon 140 of the MSH2 protein (p.Asp140Ala). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related conditions. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
All of Us Research Program, |
RCV004005106 | SCV004818652 | uncertain significance | Lynch syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing |