Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002003133 | SCV002274654 | uncertain significance | Bloom syndrome | 2022-08-29 | 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: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1483339). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (rs774551420, gnomAD 0.001%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 575 of the BLM protein (p.Ala575Val). |
| Ambry Genetics | RCV002398057 | SCV002714222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-08 | criteria provided, single submitter | clinical testing | The p.A575V variant (also known as c.1724C>T), located in coding exon 6 of the BLM gene, results from a C to T substitution at nucleotide position 1724. The alanine at codon 575 is replaced by valine, 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. |