Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000477040 | SCV000543358 | uncertain significance | Bloom syndrome | 2021-06-17 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BLM-related disease. This sequence change replaces glutamic acid with lysine at codon 768 of the BLM protein (p.Glu768Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |
| Ambry Genetics | RCV001015012 | SCV001175796 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-26 | criteria provided, single submitter | clinical testing | The p.E768K variant (also known as c.2302G>A), located in coding exon 9 of the BLM gene, results from a G to A substitution at nucleotide position 2302. The glutamic acid at codon 768 is replaced by lysine, 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. |