Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001235974 | SCV001408684 | uncertain significance | Bloom syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with serine at codon 697 of the BLM protein (p.Leu697Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is not present in population databases (ExAC 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV004951404 | SCV005538069 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-28 | criteria provided, single submitter | clinical testing | The p.L697S variant (also known as c.2090T>C), located in coding exon 8 of the BLM gene, results from a T to C substitution at nucleotide position 2090. The leucine at codon 697 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998756 | SCV005624245 | uncertain significance | not provided | 2024-11-15 | criteria provided, single submitter | clinical testing | The BLM c.2090T>C (p.Leu697Ser) variant has not been reported in individuals with BLM-related conditions 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |