This variant is classified as a variant of unknown significance because its contribution to schwannomatosis susceptibility (see 162091) has not been confirmed.
In a large family segregating autosomal dominant schwannomatosis (see 162091) in which affected family members were negative for mutations in SMARCB1 (601607), LZTR1 (600574), NF1 (613113), and NF2 (607379), Zhang et al. (2014) performed whole-genome sequencing on 2 sibs, 1 affected and 1 unaffected, and whole-exome sequencing on 3 sibs, 2 affected and 1 unaffected. The authors identified heterozygous variants in the MYPN (608517), COQ6, CKMT1A (613415), CYP11A1 (118485), DUOX1 (606758), and TRIOBP (609761) genes in all affected members. On the basis of intensive literature review and mutation prediction of these genetic variants, Zhang et al. (2014) focused on a c.622G-C transversion in the COQ6 gene, resulting in an asp208-to-his (D208H) substitution. The mutation altered an amino acid residue that is uniformly conserved from Escherichia coli to Homo sapiens, and a substitution there was predicted to interfere with the FAD-binding domain. Zhang et al. (2014) also performed studies on yeast and showed that loss of function of this gene caused COQ10 (607426) deficiency. The authors offered no plausible mechanism for oncogenesis due to the COQ6 mutation.
