Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001013978 | SCV001174628 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-02 | criteria provided, single submitter | clinical testing | The p.M1? variant (also known as c.1A>G) is located in coding exon 1 of the RAD51C gene and results from a A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). 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. |
| Labcorp Genetics |
RCV001056536 | SCV001220983 | uncertain significance | Fanconi anemia complementation group O | 2023-08-16 | 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 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: 820479). 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. |
| Color Diagnostics, |
RCV001013978 | SCV001347897 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-29 | criteria provided, single submitter | clinical testing | This variant results in the loss of the translation start codon of the RAD51C protein. However, codon 10 encodes for a methionine and it may serve as an alternative translation start codon before the first known functional domain (RAD51B/RAD51D/XRCC3 interacting domain at amino acids 79-136). A functional study suggested that the variant protein lacking the normal translation start codon can function similarly to the wild type protein (PMID: 12966089). This variant has not been reported in individuals affected with hereditary cancer 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. |
| Laboratory for Genotyping Development, |
RCV003160176 | SCV002758217 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |