Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000547450 | SCV000625605 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-03-21 | criteria provided, single submitter | clinical testing | 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. 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) 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. ClinVar contains an entry for this variant (Variation ID: 455696). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 757 of the PMS2 protein (p.Glu757Ala). |
| Ambry Genetics | RCV003159734 | SCV003883916 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-03 | criteria provided, single submitter | clinical testing | The p.E757A variant (also known as c.2270A>C), located in coding exon 13 of the PMS2 gene, results from an A to C substitution at nucleotide position 2270. The glutamic acid at codon 757 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |