Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016389 | SCV001177342 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | The p.D906V variant (also known as c.2717A>T), located in coding exon 13 of the BLM gene, results from an A to T substitution at nucleotide position 2717. The aspartic acid at codon 906 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 | RCV001860825 | SCV002153301 | uncertain significance | Bloom syndrome | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with valine at codon 906 of the BLM protein (p.Asp906Val). The aspartic acid residue is weakly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). 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: 821706). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |