Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000582599 | SCV000690342 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-09-05 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000708887 | SCV000837914 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000807532 | SCV000947589 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1103 of the MSH6 protein (p.Phe1103Val). 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: 491936). 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. 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. |
| Ambry Genetics | RCV000582599 | SCV002605655 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | The p.F1103V variant (also known as c.3307T>G), located in coding exon 5 of the MSH6 gene, results from a T to G substitution at nucleotide position 3307. The phenylalanine at codon 1103 is replaced by valine, an amino acid with highly similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). 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. |
| Baylor Genetics | RCV003459447 | SCV004195601 | uncertain significance | Endometrial carcinoma | 2023-08-09 | criteria provided, single submitter | clinical testing |