Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482039 | SCV000573285 | uncertain significance | not provided | 2023-09-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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 |
Labcorp Genetics |
RCV001219660 | SCV001391610 | uncertain significance | Fanconi anemia complementation group O | 2024-03-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 49 of the RAD51C protein (p.Glu49Lys). This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. This variant is present in population databases (rs753709131, gnomAD 0.006%). This missense change has been observed in individual(s) with ovarian cancer (PMID: 36562461). ClinVar contains an entry for this variant (Variation ID: 423572). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects RAD51C function (PMID: 36562461). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change is associated with inconclusive levels of altered splicing (Invitae). 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. |