Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001203373 | SCV001374535 | uncertain significance | Bloom syndrome | 2022-11-25 | 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: 934893). 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). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 329 of the BLM protein (p.Asp329His). |
| Ambry Genetics | RCV002379766 | SCV002695777 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-22 | criteria provided, single submitter | clinical testing | The p.D329H variant (also known as c.985G>C), located in coding exon 4 of the BLM gene, results from a G to C substitution at nucleotide position 985. The aspartic acid at codon 329 is replaced by histidine, an amino acid with 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998718 | SCV005624297 | uncertain significance | not provided | 2024-10-22 | criteria provided, single submitter | clinical testing | The BLM c.985G>C (p.Asp329His) variant has not been reported in individuals with BLM-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |