Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002623099 | SCV002978122 | uncertain significance | Bloom syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 309 of the BLM protein (p.Ile309Val). 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. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV003308204 | SCV004001014 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.I309V variant (also known as c.925A>G), located in coding exon 3 of the BLM gene, results from an A to G substitution at nucleotide position 925. The isoleucine at codon 309 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |