Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002025518 | SCV002293726 | uncertain significance | not provided | 2021-06-16 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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 MSH3-related conditions. This variant is present in population databases (rs749300303, ExAC 0.01%). This sequence change replaces phenylalanine with cysteine at codon 291 of the MSH3 protein (p.Phe291Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. |
| Ambry Genetics | RCV003170555 | SCV003856393 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-05 | criteria provided, single submitter | clinical testing | The p.F291C variant (also known as c.872T>G), located in coding exon 5 of the MSH3 gene, results from a T to G substitution at nucleotide position 872. The phenylalanine at codon 291 is replaced by cysteine, 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. |