Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000697977 | SCV000826614 | uncertain significance | Bloom syndrome | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1121 of the BLM protein (p.Ser1121Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 575684). 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 with a negative predictive value of 80%. 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 | RCV001020095 | SCV001181527 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-27 | criteria provided, single submitter | clinical testing | The p.S1121I variant (also known as c.3362G>T), located in coding exon 17 of the BLM gene, results from a G to T substitution at nucleotide position 3362. The serine at codon 1121 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is well 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478428 | SCV004222480 | uncertain significance | not provided | 2022-12-02 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000004 (1/251218 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Natera, |
RCV000697977 | SCV002090558 | uncertain significance | Bloom syndrome | 2018-09-26 | no assertion criteria provided | clinical testing |