Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000530372 | SCV000623254 | uncertain significance | Bloom syndrome | 2022-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 642 of the BLM protein (p.Glu642Lys). This variant is present in population databases (rs201458487, gnomAD 0.03%). 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: 454090). 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. 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. |
Ambry Genetics | RCV001013713 | SCV001174334 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-09 | criteria provided, single submitter | clinical testing | The p.E642K variant (also known as c.1924G>A), located in coding exon 7 of the BLM gene, results from a G to A substitution at nucleotide position 1924. The glutamic acid at codon 642 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
Natera, |
RCV000530372 | SCV001461829 | uncertain significance | Bloom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |