Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000703461 | SCV000832361 | uncertain significance | Bloom syndrome | 2018-01-13 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BLM-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 855 of the BLM protein (p.Met855Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. |
| Ambry Genetics | RCV004948624 | SCV005541090 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-15 | criteria provided, single submitter | clinical testing | The p.M855V variant (also known as c.2563A>G), located in coding exon 12 of the BLM gene, results from an A to G substitution at nucleotide position 2563. The methionine at codon 855 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |