Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000561463 | SCV000670075 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | The p.G1224R variant (also known as c.3670G>A), located in coding exon 8 of the MSH6 gene, results from a G to A substitution at nucleotide position 3670. The glycine at codon 1224 is replaced by arginine, an amino acid with dissimilar 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 | RCV003767182 | SCV004681448 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-06-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 483860). 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. 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 glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1224 of the MSH6 protein (p.Gly1224Arg). |
All of Us Research Program, |
RCV004001064 | SCV004821091 | uncertain significance | Lynch syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing |