Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820877 | SCV000961610 | uncertain significance | Bloom syndrome | 2023-06-13 | 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: 663081). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (rs761284618, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 473 of the BLM protein (p.Thr473Ile). |
| Ambry Genetics | RCV002390693 | SCV002696576 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-23 | criteria provided, single submitter | clinical testing | The p.T473I variant (also known as c.1418C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1418. The threonine at codon 473 is replaced by isoleucine, 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. |