Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000689749 | SCV000817415 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 794 of the PMS2 protein (p.Pro794Ala). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 569181). 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 with a positive predictive value of 80%. 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 | RCV002458222 | SCV002737785 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-29 | criteria provided, single submitter | clinical testing | The p.P794A variant (also known as c.2380C>G) located in coding exon 14 of the PMS2 gene. This variant results from a C to G substitution at nucleotide position 2380. The proline at codon 794 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Center for Genomic Medicine, |
RCV003320726 | SCV004025097 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing |