ClinVar

In affected members of a German family with recessive myotonia (255700), Lorenz et al. (1994) identified compound heterozygosity for 2 mutations in the CLCN1 gene: a 979G-A transition in a splice consensus site at the end of exon 8, and a 1488G-T transversion in exon 14, resulting in an arg496-to-ser (R496S; 118425.0004). Functional expression of R496S cRNA in Xenopus oocytes yielded no detectable currents. Furthermore, it did not suppress wildtype currents in coexpression assay, confirming it as a recessive mutation. The G-to-A transition in exon 8 was stated to affect the last nucleotide of the exon. If this interfered with mRNA splicing at that exon/intron boundary, the translation product would be terminated by a stop codon after 51 additional amino acids or other splice sites in the intron might be used. Alternatively, if splicing were normal, this mutation would lead to a substitution of isoleucine for valine at position 327 (V327I). Since this residue is not conserved among the members of this gene family and most members have negatively charged glutamate residues at this position, it is unlikely that such a substitution would have a dramatic effect on channel function. This would argue for an aberrant splicing as the effect of the G979A mutation.