Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000216075 | SCV000274466 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-11 | criteria provided, single submitter | clinical testing | The p.M1? variant (also known as c.3G>A), located in coding exon 1 of the RAD51C gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. This variant was reported in 2/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med 2021 02;384:428-439). Variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however, there is an in-frame methionine 9 amino acids from the initiation site, which may result in N-terminal truncation of unknown functional significance. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000579223 | SCV000680878 | uncertain significance | not provided | 2019-10-11 | criteria provided, single submitter | clinical testing | Initiation codon variant in a gene for which a downstreamin-frame ATG could serve as an alternate initiator codon (French 2003); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Observed in individuals with breast cancer (Cybulski 2019); This variant is associated with the following publications: (PMID: 12966089, 31173646) |
| Color Diagnostics, |
RCV000216075 | SCV000686349 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-21 | criteria provided, single submitter | clinical testing | This variant affects the translation start codon of the RAD51C gene and may result in an absent or non-functional protein product. However, an in-frame methionine 9 codons downstream may function as an alternative start codon and is located before the first known functional domain (RAD51B/RAD51D/XRCC3 interacting domain at amino acids 79-136) of the RAD51C protein. A functional study has shown that the RAD51C protein produced from this downstream methionine can function similarly to the wild type protein (PMID: 12966089). This variant has been reported in an individual affected with breast cancer (PMID: 31173646). This variant has been identified in 1/31396 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 | RCV000648266 | SCV000770080 | uncertain significance | Fanconi anemia complementation group O | 2022-10-31 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the RAD51C mRNA. The next in-frame methionine is located at codon 10. This variant is present in population databases (rs769053886, gnomAD 0.01%). 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: 230796). 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. |
| Mendelics | RCV000709499 | SCV000839323 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000648266 | SCV001140704 | uncertain significance | Fanconi anemia complementation group O | 2019-05-28 | criteria provided, single submitter | clinical testing |