Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000557690 | SCV000623239 | uncertain significance | Bloom syndrome | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 488 of the BLM protein (p.Glu488Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC 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: 454078). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV002395271 | SCV002696289 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-09 | criteria provided, single submitter | clinical testing | The p.E488K variant (also known as c.1462G>A), located in coding exon 6 of the BLM gene, results from a G to A substitution at nucleotide position 1462. The glutamic acid at codon 488 is replaced by lysine, 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. |
| Natera, |
RCV000557690 | SCV002090039 | uncertain significance | Bloom syndrome | 2021-07-20 | no assertion criteria provided | clinical testing |