Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001226550 | SCV001398869 | uncertain significance | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | 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 sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 469 of the MSH3 protein (p.Phe469Leu). This variant is present in population databases (rs761160657, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 954146). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV003284080 | SCV004008636 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-16 | criteria provided, single submitter | clinical testing | The p.F469L variant (also known as c.1405T>C), located in coding exon 9 of the MSH3 gene, results from a T to C substitution at nucleotide position 1405. The phenylalanine at codon 469 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |