Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115620 | SCV000149529 | uncertain significance | not provided | 2014-02-11 | criteria provided, single submitter | clinical testing | This variant is denoted BARD1 c.1867G>C at the cDNA level, p.Gly623Arg (G623R) at the protein level, and results in the change of a Glycine to an Arginine (GGG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BARD1 Gly623Arg 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 non-conservative substitution in which a neutral non-polar amino acid is replaced with a positive polar one, altering a position that is well conserved throughout evolution and is located in the BRCT1 domain. Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on currently available information, it is unclear whether BARD1 Gly623Arg is a pathogenic variant or a benign variant Furthermore, BARD1 has been only recently described in association with cancer predisposition and the risks are not well understood. |
Invitae | RCV000468071 | SCV000545558 | uncertain significance | Familial cancer of breast | 2019-09-19 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. 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 disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BARD1-related disease. ClinVar contains an entry for this variant (Variation ID: 127724). This sequence change replaces glycine with arginine at codon 623 of the BARD1 protein (p.Gly623Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |