Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568285 | SCV000662426 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-23 | criteria provided, single submitter | clinical testing | The p.F596Y variant (also known as c.1787T>A), located in coding exon 4 of the MSH6 gene, results from a T to A substitution at nucleotide position 1787. The phenylalanine at codon 596 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the CoDP in silico tool predicts this alteration to have a minor impact on molecular function, with a score of 0.020 (Terui H et al. J Biomed Sci. 2013;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000629691 | SCV000750647 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-08-29 | criteria provided, single submitter | clinical testing | 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: 479879). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 596 of the MSH6 protein (p.Phe596Tyr). |
| Genetic Services Laboratory, |
RCV001821658 | SCV002069110 | uncertain significance | not specified | 2018-03-12 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004569114 | SCV005054931 | uncertain significance | Endometrial carcinoma | 2024-02-09 | criteria provided, single submitter | clinical testing |