Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001225612 | SCV001397896 | pathogenic | Bloom syndrome | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu394Glyfs*23) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is present in population databases (rs758132052, gnomAD 0.003%). 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: 953335). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV003284079 | SCV004003079 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-04-20 | criteria provided, single submitter | clinical testing | The c.1180_1181delTT pathogenic mutation, located in coding exon 5 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 1180 to 1181, causing a translational frameshift with a predicted alternate stop codon (p.L394Gfs*23). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |