Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001056005 | SCV001220423 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-03-26 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MSH2 protein function. 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 has not been reported in the literature in individuals with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 851580). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 922 of the MSH2 protein (p.Phe922Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. |
All of Us Research Program, |
RCV004000077 | SCV004818875 | uncertain significance | Lynch syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with serine at codon 922 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |