Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001350923 | SCV001545351 | uncertain significance | Bloom syndrome | 2023-05-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1046370). 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. 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 alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1206 of the BLM protein (p.Ala1206Glu). |
| Ambry Genetics | RCV003294380 | SCV004001015 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | clinical testing | The p.A1206E variant (also known as c.3617C>A), located in coding exon 18 of the BLM gene, results from a C to A substitution at nucleotide position 3617. The alanine at codon 1206 is replaced by glutamic acid, an amino acid with dissimilar 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. |