Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000628681 | SCV000749587 | uncertain significance | Bloom syndrome | 2022-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 854 of the BLM protein (p.Ser854Asn). This variant is present in population databases (rs758692622, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 31780696). ClinVar contains an entry for this variant (Variation ID: 524813). 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. 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. |
Mendelics | RCV000628681 | SCV000838974 | uncertain significance | Bloom syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001015940 | SCV001176835 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-26 | criteria provided, single submitter | clinical testing | The p.S854N variant (also known as c.2561G>A), located in coding exon 12 of the BLM gene, results from a G to A substitution at nucleotide position 2561. The serine at codon 854 is replaced by asparagine, an amino acid with highly similar properties. This alteration was identified in a cohort of Puerto Rican breast cancer patients (Dutil J et al. Sci Rep. 2019 11;9:17769). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478339 | SCV004222456 | uncertain significance | not provided | 2022-11-25 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000087 (3/34498 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 31780696 (2019)). 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, |
RCV000628681 | SCV002088087 | uncertain significance | Bloom syndrome | 2018-12-26 | no assertion criteria provided | clinical testing |