Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000233856 | SCV000291237 | uncertain significance | Fanconi anemia complementation group O | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 229 of the RAD51C protein (p.Phe229Leu). This variant is present in population databases (rs780177888, gnomAD 0.0009%). This missense change has been observed in individual(s) with aplastic anemia, but was also reported in an unaffected individual (PMID: 24763404). ClinVar contains an entry for this variant (Variation ID: 241774). 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 with a negative predictive value of 80%. 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506053 | SCV000602142 | uncertain significance | not specified | 2017-06-16 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000574742 | SCV000671904 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-21 | criteria provided, single submitter | clinical testing | The p.F229L variant (also known as c.687C>G), located in coding exon 4 of the RAD51C gene, results from a C to G substitution at nucleotide position 687. The phenylalanine at codon 229 is replaced by leucine, an amino acid with highly similar properties. In one study, this variant was reported in 1/45 patients with idiopathic aplastic anemia (Collopy LC et al. Haematologica. 2014 Jul;99:e109-11). This amino acid position is highly 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. |
Color Diagnostics, |
RCV000574742 | SCV001345791 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-21 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with leucine at codon 229 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with idiopathic aplastic anemia (PMID: 24763404). This variant has been identified in 2/251196 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |