Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000819972 | SCV000960661 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 285 of the PMS2 protein (p.Thr285Lys). This variant is not present in population databases (gnomAD no frequency). 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: 662352). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PMS2 protein function. 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 | RCV003353058 | SCV004054915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-27 | criteria provided, single submitter | clinical testing | The p.T285K variant (also known as c.854C>A), located in coding exon 8 of the PMS2 gene, results from a C to A substitution at nucleotide position 854. The threonine at codon 285 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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. |