Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001238321 | SCV001411125 | uncertain significance | Bloom syndrome | 2023-06-30 | 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) performed at Invitae indicates that this missense variant is expected to disrupt BLM protein function. ClinVar contains an entry for this variant (Variation ID: 964153). 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 isoleucine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1005 of the BLM protein (p.Ile1005Lys). |
| Ambry Genetics | RCV002436937 | SCV002753352 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.I1005K variant (also known as c.3014T>A), located in coding exon 14 of the BLM gene, results from a T to A substitution at nucleotide position 3014. The isoleucine at codon 1005 is replaced by lysine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |