Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002425827 | SCV002729575 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-01 | criteria provided, single submitter | clinical testing | The p.L737M variant (also known as c.2209C>A), located in coding exon 9 of the BLM gene, results from a C to A substitution at nucleotide position 2209. The leucine at codon 737 is replaced by methionine, an amino acid with highly 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. |
| Labcorp Genetics |
RCV003098715 | SCV003456220 | pathogenic | Bloom syndrome | 2022-09-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu737Met) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). 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. 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. For these reasons, this variant has been classified as Pathogenic. |