Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002600102 | SCV002939251 | uncertain significance | Bloom syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 714 of the BLM protein (p.Ser714Cys). This variant is present in population databases (rs764488484, 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: 1909124). 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%. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003477010 | SCV004222445 | uncertain significance | not provided | 2023-06-21 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in an individual with colorectal cancer who had a family history of different cancer types including breast and colorectal cancers (PMID: 32449991 (2020)). The frequency of this variant in the general population, 0.000004 (1/251412 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the 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 damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Mendelics | RCV003492771 | SCV004232596 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing |