Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216592 | SCV000272986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.H139R variant (also known as c.416A>G), located in coding exon 5 of the PMS2 gene, results from an A to G substitution at nucleotide position 416. The histidine at codon 139 is replaced by arginine, an amino acid with highly similar properties. Based on protein sequence alignment, 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 | RCV002518233 | SCV003348596 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-07-19 | 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) 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: 229687). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 139 of the PMS2 protein (p.His139Arg). |