Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017571 | SCV001178665 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-13 | criteria provided, single submitter | clinical testing | The p.R979K variant (also known as c.2936G>A), located in coding exon 14 of the BLM gene, results from a G to A substitution at nucleotide position 2936. The arginine at codon 979 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001860870 | SCV002226400 | uncertain significance | Bloom syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BLM-related conditions. This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 979 of the BLM protein (p.Arg979Lys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 822308). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BLM protein function. 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. |