Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000116182 | SCV000150091 | uncertain significance | not provided | 2014-02-10 | criteria provided, single submitter | clinical testing | This variant is denoted RAD51C c.959A>G at the cDNA level, p.Lys320Arg (K320R) at the protein level, and results in the change of a Lysine to an Arginine (AAG>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Lys320Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a conservative substitution of one positive polar amino acid for another, altering a position that is moderately conserved throughout evolution and is not located in a known functional domain (Uniprot). In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider RAD51C Lys320Arg to be a variant of uncertain significance. Furthermore, RAD51C has been only recently described in association with cancer predisposition and the risks are not well understood. |
Labcorp Genetics |
RCV001854563 | SCV002270493 | uncertain significance | Fanconi anemia complementation group O | 2022-01-26 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 128213). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 320 of the RAD51C protein (p.Lys320Arg). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230405 | SCV003928647 | uncertain significance | not specified | 2023-04-04 | criteria provided, single submitter | clinical testing |