Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001372046 | SCV001568634 | uncertain significance | Bloom syndrome | 2020-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 624 of the BLM protein (p.Gln624Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BLM-related conditions. 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. 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 | RCV002413892 | SCV002722320 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.Q624R variant (also known as c.1871A>G), located in coding exon 6 of the BLM gene, results from an A to G substitution at nucleotide position 1871. The glutamine at codon 624 is replaced by arginine, an amino acid with highly 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. |