Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001021448 | SCV001183065 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-04 | criteria provided, single submitter | clinical testing | The p.G1308R variant (also known as c.3922G>C), located in coding exon 20 of the BLM gene, results from a G to C substitution at nucleotide position 3922. The glycine at codon 1308 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001303467 | SCV001492714 | uncertain significance | Bloom syndrome | 2023-03-04 | 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. 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 not expected to disrupt BLM protein function. ClinVar contains an entry for this variant (Variation ID: 824387). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1308 of the BLM protein (p.Gly1308Arg). |