Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001963442 | SCV002250051 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-09-20 | 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 expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 1464343). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 205 of the PMS2 protein (p.Gln205His). |
| Ambry Genetics | RCV002352665 | SCV002655764 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-05 | criteria provided, single submitter | clinical testing | The p.Q205H variant (also known as c.615G>C), located in coding exon 6 of the PMS2 gene, results from a G to C substitution at nucleotide position 615. The glutamine at codon 205 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Baylor Genetics | RCV003471203 | SCV004205451 | uncertain significance | Lynch syndrome 4 | 2023-09-11 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004011000 | SCV004828462 | uncertain significance | Lynch syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing |