Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010775 | SCV001171015 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-27 | criteria provided, single submitter | clinical testing | The p.T430R variant (also known as c.1289C>G), located in coding exon 11 of the PMS2 gene, results from a C to G substitution at nucleotide position 1289. The threonine at codon 430 is replaced by arginine, an amino acid with similar properties. This amino acid position is poorly 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. |
| Invitae | RCV001860650 | SCV002186667 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-08-05 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 818812). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with arginine at codon 430 of the PMS2 protein (p.Thr430Arg). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and arginine. |