Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002447829 | SCV002678910 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-16 | criteria provided, single submitter | clinical testing | The p.S285N variant (also known as c.854G>A), located in coding exon 4 of the MSH6 gene, results from a G to A substitution at nucleotide position 854. The serine at codon 285 is replaced by asparagine, an amino acid with highly similar properties. This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003099968 | SCV002978881 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-08-27 | 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 not expected to disrupt MSH6 protein function. 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 serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 285 of the MSH6 protein (p.Ser285Asn). |
Baylor Genetics | RCV004572388 | SCV005054917 | uncertain significance | Endometrial carcinoma | 2024-02-16 | criteria provided, single submitter | clinical testing |