Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001014324 | SCV001175018 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-11 | criteria provided, single submitter | clinical testing | The p.Y707H variant (also known as c.2119T>C), located in coding exon 12 of the PMS2 gene, results from a T to C substitution at nucleotide position 2119. The tyrosine at codon 707 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV001037162 | SCV001200561 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-03 | 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 expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 820656). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. 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. This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 707 of the PMS2 protein (p.Tyr707His). |