Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000565395 | SCV000667116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-23 | criteria provided, single submitter | clinical testing | The p.I64F variant (also known as c.190A>T), located in coding exon 2 of the RAD51C gene, results from an A to T substitution at nucleotide position 190. The isoleucine at codon 64 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly 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, |
RCV000565395 | SCV000905048 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with phenylalanine at codon 64 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251426 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. |
Invitae | RCV000801716 | SCV000941508 | uncertain significance | Fanconi anemia complementation group O | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 64 of the RAD51C protein (p.Ile64Phe). This variant is present in population databases (rs770335248, gnomAD 0.0009%). 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: 482168). 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. |
Gene |
RCV001779013 | SCV002015760 | uncertain significance | not provided | 2021-11-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003962628 | SCV004785257 | uncertain significance | RAD51C-related condition | 2024-01-19 | criteria provided, single submitter | clinical testing | The RAD51C c.190A>T variant is predicted to result in the amino acid substitution p.Ile64Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD and has been interpreted as variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/482168/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |