Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485141 | SCV000571563 | uncertain significance | not provided | 2016-09-01 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.320G>C at the cDNA level, p.Arg107Pro (R107P) at the protein level, and results in the change of an Arginine to a Proline (CGG>CCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Arg107Pro was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PMS2 Arg107Pro occurs at a position that is conserved across species and is located within the ATPase domain (Guarne 2001, Fukui 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether PMS2 Arg107Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000568205 | SCV000670849 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-22 | criteria provided, single submitter | clinical testing | The p.R107P variant (also known as c.320G>C), located in coding exon 4 of the PMS2 gene, results from a G to C substitution at nucleotide position 320. The arginine at codon 107 is replaced by proline, an amino acid with dissimilar 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. |
Color Diagnostics, |
RCV000568205 | SCV000910242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing |