Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000708873 | SCV000837894 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001861935 | SCV002296659 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-09-02 | criteria provided, single submitter | clinical testing | 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: 584618). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 727 of the MSH6 protein (p.Thr727Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Ambry Genetics | RCV003165936 | SCV003865241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-27 | criteria provided, single submitter | clinical testing | The p.T727I variant (also known as c.2180C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 2180. The threonine at codon 727 is replaced by isoleucine, an amino acid with similar properties. This variant has been identified as somatic in a proband with colorectal cancer (Berginc G et al. Fam Cancer, 2009 Jun;8:421-9). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |