Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003613981 | SCV004438058 | uncertain significance | Bloom syndrome | 2023-02-09 | 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 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). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 919 of the BLM protein (p.His919Asp). |
| Ambry Genetics | RCV004604996 | SCV005101911 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-24 | criteria provided, single submitter | clinical testing | The p.H919D variant (also known as c.2755C>G), located in coding exon 13 of the BLM gene, results from a C to G substitution at nucleotide position 2755. The histidine at codon 919 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |