Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220063 | SCV000277444 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-31 | criteria provided, single submitter | clinical testing | The p.D1181G variant (also known as c.3542A>G), located in coding exon 6 of the MSH6 gene, results from an A to G substitution at nucleotide position 3542. The aspartic acid at codon 1181 is replaced by glycine, an amino acid with similar 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. |
Invitae | RCV000808376 | SCV000948484 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-04-28 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 233132). 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 glycine, which is neutral and non-polar, at codon 1181 of the MSH6 protein (p.Asp1181Gly). |
All of Us Research Program, |
RCV003998031 | SCV004821996 | uncertain significance | Lynch syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing |