Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001018337 | SCV001179562 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-18 | criteria provided, single submitter | clinical testing | The p.H1019P variant (also known as c.3056A>C), located in coding exon 15 of the BLM gene, results from an A to C substitution at nucleotide position 3056. The histidine at codon 1019 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV001239564 | SCV001412447 | uncertain significance | Bloom syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1019 of the BLM protein (p.His1019Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 822740). 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 with a positive predictive value of 80%. 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. |
Natera, |
RCV001239564 | SCV002090509 | uncertain significance | Bloom syndrome | 2020-08-17 | no assertion criteria provided | clinical testing |