Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001364890 | SCV001561085 | uncertain significance | Bloom syndrome | 2020-06-23 | 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BLM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 787 of the BLM protein (p.Lys787Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. |
| Ambry Genetics | RCV004601479 | SCV005101935 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-23 | criteria provided, single submitter | clinical testing | The p.K787E variant (also known as c.2359A>G), located in coding exon 10 of the BLM gene, results from an A to G substitution at nucleotide position 2359. The lysine at codon 787 is replaced by glutamic acid, 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. Based on the available evidence, the clinical significance of this variant remains unclear. |