Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010341 | SCV001170522 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-29 | criteria provided, single submitter | clinical testing | The p.P404L variant (also known as c.1211C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1211. The proline at codon 404 is replaced by leucine, an amino acid with similar properties. 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. |
| Invitae | RCV001862765 | SCV002261628 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-04-19 | 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 PMS2 protein function. This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 818600). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 404 of the PMS2 protein (p.Pro404Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. |