Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167462 | SCV000218318 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-12-24 | criteria provided, single submitter | clinical testing | Thep.S20Cvariant (also known as c.59C>G), located in coding exon 1 of theRAD51Cgene, results from a C to G substitution at nucleotide position 59. The serine at codon 20 is replaced by cysteine, an amino acid with dissimilar 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 0.003% (greater than 40000 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 benign but deleterious by PolyPhen and SIFTin silicoanalyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.S20C remains unclear. |
| Invitae | RCV000704412 | SCV000833361 | uncertain significance | Fanconi anemia complementation group O | 2023-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 20 of the RAD51C protein (p.Ser20Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 187712). 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. 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. |