Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001068587 | SCV001233709 | uncertain significance | Bloom syndrome | 2020-02-26 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces lysine with arginine at codon 138 of the BLM protein (p.Lys138Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine 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. |
| Ambry Genetics | RCV004950248 | SCV005544537 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-02 | criteria provided, single submitter | clinical testing | The p.K138R variant (also known as c.413A>G), located in coding exon 2 of the BLM gene, results from an A to G substitution at nucleotide position 413. The lysine at codon 138 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. Based on the available evidence, the clinical significance of this variant remains unclear. |