Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001184690 | SCV001350726 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-21 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 533 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001184690 | SCV002709749 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-06 | criteria provided, single submitter | clinical testing | The p.V533M variant (also known as c.1597G>A), located in coding exon 11 of the PMS2 gene, results from a G to A substitution at nucleotide position 1597. The valine at codon 533 is replaced by methionine, an amino acid with highly 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. |