Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001233184 | SCV001405767 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2019-07-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RAD51D-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with proline at codon 129 of the RAD51D protein (p.Gln129Pro). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and proline. |
Ambry Genetics | RCV002366038 | SCV002624237 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-10-19 | criteria provided, single submitter | clinical testing | The p.Q129P variant (also known as c.386A>C), located in coding exon 5 of the RAD51D gene, results from an A to C substitution at nucleotide position 386. The glutamine at codon 129 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 53000 alleles tested) in our clinical cohort.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 p.Q129P remains unclear. |