Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001040055 | SCV001203610 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-06-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1185 of the MSH6 protein (p.Ser1185Pro). This variant is not present in population databases (gnomAD no frequency). 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. ClinVar contains an entry for this variant (Variation ID: 838498). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. |
Ambry Genetics | RCV002454286 | SCV002617326 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-10 | criteria provided, single submitter | clinical testing | The p.S1185P variant (also known as c.3553T>C), located in coding exon 6 of the MSH6 gene, results from a T to C substitution at nucleotide position 3553. The serine at codon 1185 is replaced by proline, an amino acid with similar properties. This amino acid position is well 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. |
All of Us Research Program, |
RCV004004729 | SCV004835381 | uncertain significance | Lynch syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |