Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001916169 | SCV002178183 | pathogenic | Bloom syndrome | 2020-11-06 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals with BLM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp1288*) 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). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV001916169 | SCV005058117 | likely pathogenic | Bloom syndrome | 2024-03-29 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004946865 | SCV005538060 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-12-03 | criteria provided, single submitter | clinical testing | The p.W1288* pathogenic mutation (also known as c.3863G>A), located in coding exon 19 of the BLM gene, results from a G to A substitution at nucleotide position 3863. This changes the amino acid from a tryptophan to a stop codon within coding exon 19. 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. |