Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002305061 | SCV002591782 | uncertain significance | Bloom syndrome | 2023-05-09 | 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: 1719938). 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 415 of the BLM protein (p.Asp415His). |
| Ambry Genetics | RCV004948694 | SCV005544594 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-27 | criteria provided, single submitter | clinical testing | The p.D415H variant (also known as c.1243G>C), located in coding exon 6 of the BLM gene, results from a G to C substitution at nucleotide position 1243. The aspartic acid at codon 415 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. Based on the available evidence, the clinical significance of this variant remains unclear. |