Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570196 | SCV000667114 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-29 | criteria provided, single submitter | clinical testing | The p.A300V variant (also known as c.899C>T), located in coding exon 6 of the RAD51C gene, results from a C to T substitution at nucleotide position 899. The alanine at codon 300 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV000648222 | SCV000770036 | uncertain significance | Fanconi anemia complementation group O | 2024-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 300 of the RAD51C protein (p.Ala300Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 33646313). ClinVar contains an entry for this variant (Variation ID: 482166). Invitae Evidence 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 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. |
Prevention |
RCV004530604 | SCV004115617 | uncertain significance | RAD51C-related disorder | 2023-05-09 | criteria provided, single submitter | clinical testing | The RAD51C c.899C>T variant is predicted to result in the amino acid substitution p.Ala300Val. This alteration has been reported as a variant of uncertain significance in individuals with cancer (breast, endometrial; George et al. 2021. PubMed ID: 33646313; Ring et al. 2016. PubMed ID: 27443514). In ClinVar this change is classified as uncertain by multiple labs (https://preview.ncbi.nlm.nih.gov/clinvar/variation/482166/). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Baylor Genetics | RCV004569164 | SCV005053975 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-12-02 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005018979 | SCV005649742 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2024-05-28 | criteria provided, single submitter | clinical testing |