Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000545838 | SCV000624754 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-11-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 455194). 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. 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 disruptive. This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 793 of the MSH6 protein (p.Asp793His). |
| Ambry Genetics | RCV002448603 | SCV002735077 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-12 | criteria provided, single submitter | clinical testing | The p.D793H variant (also known as c.2377G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 2377. The aspartic acid at codon 793 is replaced by histidine, an amino acid with similar 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. |
| All of Us Research Program, |
RCV004003677 | SCV004814458 | uncertain significance | Lynch syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing |