DMD Open‐access Variant Explorer (DOVE): A scalable, open‐access, web‐based tool to aid in clinical interpretation of genetic variants in the DMD gene

Abstract

Background Duchenne muscular dystrophy (Duchenne) is caused by pathogenic variants in the DMD gene. Antisense oligonucleotides (AONs) are one emerging precision medicine treatment for Duchenne. DMD molecular genetic testing results guide precision‐therapy molecular eligibility, requiring healthcare providers to perform analyses currently uncommon in clinical laboratory and medical practices. Clear DMD variant notation and interpretation are key components of clinical care with the availability of precision medicine. Methods The DMD Open‐access Variant Explorer (DOVE) is a web‐based aid for DMD variant interpretation which additionally reports variant‐specific predicted molecular eligibility for therapy. DOVE was developed in Python and adapted to the Django Web framework, integrates existing open‐access tools, and does not rely on previous variant report/classification. Results DOVE [http://www.dmd.nl/DOVE] interprets colloquial and HGMD inputs of DMD variants to output HGMD variant nomenclature, theoretical molecular eligibility for therapy, and any predicted deleterious molecular consequences of therapy. DOVE relies on holistic in silico prediction of molecular eligibility for therapy in lieu of reference to an empirically defined, “variant‐eligible” list. Examples illustrate the advantage and necessity for holistic variant interpretation. Conclusion DOVE may prove useful for variant interpretation both at patient‐level and in large‐scale programs such as newborn screening and has broad application in concept to molecular genetic test result interpretation.

The Role of Dystrophin Gene Mutations in Neuropsychological Domains of DMD Boys: A Longitudinal Study

“…Bailey et al have recently developed a bioinformatics tool, called DMD Open access Variant Explorer (DOVE), to facilitate effective analysis of pathologic DMD gene variants, resulting in scope of precision medicine treatment for DMD. 27 The functional improvement observed during the follow-up period shows that boys with DMD may be more amenable to neurocognitive rehabilitation. The substantial economic burden of physical and neuro-developmental disability makes DMD patients vulnerable.…”

“…Bailey et al have recently developed a bioinformatics tool, called DMD Open access Variant Explorer (DOVE), to facilitate effective analysis of pathologic DMD gene variants, resulting in scope of precision medicine treatment for DMD. 27 …”

Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

“…Age at loss of ambulation was evaluated using a log-rank test, and the median age at loss of ambulation was estimated using the Kaplan-Meier estimator. Exon locations and stop codon types were deduced from the STRIDE Registry mutation data collected using the online mutational analysis DMD Open-access Variant Explorer tool (www.dmd.nl/DOVE/) [29].…”

Variant Impact Predictor database (VIPdb), version 2: Trends from 25 years of genetic variant impact predictors

“…Subsequently, we examined the literature and included only programs capable of handling variant data, such as VCF files, rsID, or location in the genome, and providing evidence or predictions of the variant impacts. Overall, this resulted in the identification of 186 additional VIPs, augmenting the VIPdb to a total of 403 VIPs (16, 17, 19, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 9 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233) (11,18,20,234,235,236,237,238,239,240,241,242,243,244,245,246,247,248,249,250,251,252,253,254,255,256,257,258,259,…”