Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000456520 | SCV000543384 | uncertain significance | Bloom syndrome | 2022-07-05 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1308 of the BLM protein (p.Gly1308Glu). This variant is present in population databases (rs750865930, gnomAD 0.002%). 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: 405320). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV001021449 | SCV001183066 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-27 | criteria provided, single submitter | clinical testing | The p.G1308E variant (also known as c.3923G>A), located in coding exon 20 of the BLM gene, results from a G to A substitution at nucleotide position 3923. The glycine at codon 1308 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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, |
RCV000456520 | SCV002090626 | uncertain significance | Bloom syndrome | 2020-12-29 | no assertion criteria provided | clinical testing |