Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000804098 | SCV000943992 | uncertain significance | Bloom syndrome | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1214 of the BLM protein (p.Met1214Thr). 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. ClinVar contains an entry for this variant (Variation ID: 649215). 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. 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 | RCV002345804 | SCV002619339 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-31 | criteria provided, single submitter | clinical testing | The p.M1214T variant (also known as c.3641T>C), located in coding exon 18 of the BLM gene, results from a T to C substitution at nucleotide position 3641. The methionine at codon 1214 is replaced by threonine, an amino acid with 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. |
Natera, |
RCV000804098 | SCV002090593 | uncertain significance | Bloom syndrome | 2020-07-05 | no assertion criteria provided | clinical testing |