Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004995319 | SCV005566502 | likely pathogenic | Cardiovascular phenotype | 2024-10-05 | criteria provided, single submitter | clinical testing | The c.5586+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 39 of the DMD gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown; however, the impacted region is critical for protein function (Ambry internal data). This variant has been detected in an individual reported to have Becker muscular dystrophy (Zhao L et al. Orphanet J Rare Dis, 2024 Aug;19:311). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |