Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000579830 | SCV000686355 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000817856 | SCV000958439 | uncertain significance | Fanconi anemia complementation group O | 2023-05-30 | 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 RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 490127). This missense change has been observed in individual(s) with breast cancer (PMID: 30426508). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 152 of the RAD51C protein (p.Ala152Ser). |
Ambry Genetics | RCV000579830 | SCV001184445 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-30 | criteria provided, single submitter | clinical testing | The p.A152S variant (also known as c.454G>T), located in coding exon 3 of the RAD51C gene, results from a G to T substitution at nucleotide position 454. The alanine at codon 152 is replaced by serine, an amino acid with similar properties. This variant was detected in 1/237 individuals considered high risk for hereditary breast and/or ovarian cancer that previously tested negative for pathogenic BRCA1/2 mutations (Schubert S et al. Int J Cancer, 2019 06;144:2683-2694). 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. |