Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000703164 | SCV000832051 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-05-05 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with arginine at codon 824 of the PMS2 protein (p.Thr824Arg). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and arginine. The frequency data for this variant in the population databases is considered unreliable, due to the presence of a pseudogene that has strong homology to this region. This variant has not been reported in the literature in individuals with PMS2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV003279025 | SCV004005575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-24 | criteria provided, single submitter | clinical testing | The p.T824R variant (also known as c.2471C>G), located in coding exon 15 of the PMS2 gene, results from a C to G substitution at nucleotide position 2471. The threonine at codon 824 is replaced by arginine, 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. |