Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000554295 | SCV000624815 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-03-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1027 of the MSH6 protein (p.Val1027Gly). 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: 455230). 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 with a negative 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985839 | SCV001134421 | uncertain significance | not provided | 2019-03-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002319523 | SCV002606827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-11 | criteria provided, single submitter | clinical testing | The p.V1027G variant (also known as c.3080T>G), located in coding exon 4 of the MSH6 gene, results from a T to G substitution at nucleotide position 3080. The valine at codon 1027 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Baylor Genetics | RCV004568707 | SCV005054864 | uncertain significance | Endometrial carcinoma | 2024-03-08 | criteria provided, single submitter | clinical testing |