Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001342026 | SCV001535927 | uncertain significance | Bloom syndrome | 2022-02-20 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1038686). This variant has not been reported in the literature in individuals affected with BLM-related conditions. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 420 of the BLM protein (p.Asp420His). |
| Ambry Genetics | RCV003294346 | SCV004001020 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-22 | criteria provided, single submitter | clinical testing | The p.D420H variant (also known as c.1258G>C), located in coding exon 6 of the BLM gene, results from a G to C substitution at nucleotide position 1258. The aspartic acid at codon 420 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |