Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001361379 | SCV001557354 | uncertain significance | Bloom syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with BLM-related conditions. 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: 1053081). This variant is present in population databases (rs771686396, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1382 of the BLM protein (p.Ala1382Pro). |
| Ambry Genetics | RCV002329360 | SCV002628934 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-21 | criteria provided, single submitter | clinical testing | The p.A1382P variant (also known as c.4144G>C), located in coding exon 21 of the BLM gene, results from a G to C substitution at nucleotide position 4144. The alanine at codon 1382 is replaced by proline, an amino acid with highly similar 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. |