Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016429 | SCV001177385 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | The p.D911V variant (also known as c.2732A>T), located in coding exon 13 of the BLM gene, results from an A to T substitution at nucleotide position 2732. The aspartic acid at codon 911 is replaced by valine, an amino acid with highly dissimilar 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. |
Invitae | RCV001295343 | SCV001484260 | uncertain significance | Bloom syndrome | 2022-11-22 | 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 not expected to disrupt BLM protein function. ClinVar contains an entry for this variant (Variation ID: 821731). 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 aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 911 of the BLM protein (p.Asp911Val). |
Gene |
RCV002264994 | SCV002547015 | uncertain significance | not provided | 2022-01-05 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV001295343 | SCV002088113 | uncertain significance | Bloom syndrome | 2020-07-14 | no assertion criteria provided | clinical testing |