Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016295 | SCV001177235 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-18 | criteria provided, single submitter | clinical testing | The p.L896F variant (also known as c.2686C>T), located in coding exon 13 of the BLM gene, results from a C to T substitution at nucleotide position 2686. The leucine at codon 896 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001211352 | SCV001382889 | uncertain significance | Bloom syndrome | 2023-04-14 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function. ClinVar contains an entry for this variant (Variation ID: 821663). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is present in population databases (rs151309611, gnomAD 0.007%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 896 of the BLM protein (p.Leu896Phe). |