Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002410278 | SCV002711996 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-14 | criteria provided, single submitter | clinical testing | The p.D606V variant (also known as c.1817A>T), located in coding exon 6 of the BLM gene, results from an A to T substitution at nucleotide position 1817. The aspartic acid at codon 606 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |
| Labcorp Genetics |
RCV003097273 | SCV003021846 | uncertain significance | Bloom syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 606 of the BLM protein (p.Asp606Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected 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. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003476993 | SCV004222438 | uncertain significance | not provided | 2023-07-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |