Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000628648 | SCV000749552 | uncertain significance | Bloom syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 827 of the BLM protein (p.Met827Lys). This variant is present in population databases (rs748250819, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 524784). 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 expected to disrupt BLM protein function with a positive predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
| Fulgent Genetics, |
RCV000628648 | SCV000896484 | uncertain significance | Bloom syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001015648 | SCV001176505 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-12 | criteria provided, single submitter | clinical testing | The p.M827K variant (also known as c.2480T>A), located in coding exon 11 of the BLM gene, results from a T to A substitution at nucleotide position 2480. The methionine at codon 827 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |