Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000575562 | SCV000676167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-31 | criteria provided, single submitter | clinical testing | The p.E398Q variant (also known as c.1192G>C), located in coding exon 11 of the PMS2 gene, results from a G to C substitution at nucleotide position 1192. The glutamic acid at codon 398 is replaced by glutamine, an amino acid with highly 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. |
Invitae | RCV000629728 | SCV000750684 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-18 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 486923). This missense change has been observed in individual(s) with juvenile hamartomatous polyps (PMID: 27146957). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 398 of the PMS2 protein (p.Glu398Gln). |
Color Diagnostics, |
RCV000575562 | SCV000913141 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-05 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004001199 | SCV004839839 | uncertain significance | Lynch syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing |