Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002014164 | SCV002307474 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 1174 of the MSH6 protein (p.Phe1174Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1510838). 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 MSH6 protein function with a positive predictive value of 95%. 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. |
| Ambry Genetics | RCV002458990 | SCV002613259 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | The p.F1174C variant (also known as c.3521T>G), located in coding exon 6 of the MSH6 gene, results from a T to G substitution at nucleotide position 3521. The phenylalanine at codon 1174 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Baylor Genetics | RCV003464388 | SCV004195788 | uncertain significance | Endometrial carcinoma | 2023-05-11 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004011135 | SCV004817110 | uncertain significance | Lynch syndrome | 2023-05-08 | criteria provided, single submitter | clinical testing |