Background Clinicians are faced with unprecedented opportunities to identify the genetic aetiologies of hitherto molecularly uncharacterised conditions via the use of high-throughput sequencing. Access to genomic technology and resultant data is no longer limited to clinicians, geneticists and bioinformaticians, however; ongoing commercialisation gives patients themselves ever greater access to sequencing services. We report an increasingly common medical scenario by describing two neuromuscular patients—a mother and adult son—whose consumer access to whole-genome sequencing affected their diagnostic journey.

Results Whole-genome sequencing initiated by the patients—to predict their risk of common diseases—revealed that they share several variants potentially relevant to neuromuscular diseases, which initially sidetracked diagnostic efforts. Since eventual clinical reassessment, including muscle imaging, pointed towards Bethlem myopathy, a collagen VI-related myopathy, we pursued Sanger sequencing of COL6A1, COL6A2 and COL6A3. This targeted approach revealed a heterozygous causative variant in COL6A3 (c.6365G>T (p.Gly2122Val)), shared by both individuals, that was not flagged by the interpretation of the whole-genome sequencing data.

Conclusions This report highlights the essential interplay of clinical and genomic expertise in realising the potential of high-throughput sequencing. In an era when patients themselves may bring their own data to the table, definitively identifying clinically significant genomic variants will require close collaboration among clinicians, geneticists and bioinformaticians.