Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002344400 | SCV002646553 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-21 | criteria provided, single submitter | clinical testing | The p.L400V variant (also known as c.1198C>G), located in coding exon 5 of the BLM gene, results from a C to G substitution at nucleotide position 1198. The leucine at codon 400 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003102714 | SCV003030663 | uncertain significance | Bloom syndrome | 2022-09-26 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BLM protein function. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 400 of the BLM protein (p.Leu400Val). |