Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129608 | SCV000184395 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-29 | criteria provided, single submitter | clinical testing | The p.T288A variant (also known as c.862A>G), located in coding exon 6 of the RAD51C gene, results from an A to G substitution at nucleotide position 862. The threonine at codon 288 is replaced by alanine, an amino acid with similar properties. 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. |
Counsyl | RCV000410493 | SCV000489899 | uncertain significance | Fanconi anemia complementation group O | 2016-07-21 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000411492 | SCV000489900 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2016-07-21 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000986013 | SCV001134791 | uncertain significance | not provided | 2019-03-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000410493 | SCV002213604 | uncertain significance | Fanconi anemia complementation group O | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 288 of the RAD51C protein (p.Thr288Ala). 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: 141205). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Myriad Genetics, |
RCV000411492 | SCV004019941 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-04-05 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Color Diagnostics, |
RCV000129608 | SCV004357132 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-16 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 288 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 RAD51C-related disorders in the literature. This variant has not been identified 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. |