ClinVar

Description

The Y154X pathogenic variant in the GJB1 gene has been previously reported in association with CMTX1 (Bone et al., 1997). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating is it not a common benign variant in these populations. It is predicted to cause loss of normal protein function through protein truncation as the last 130 amino acid residues are lost. This result is suggestive of mosaicism for the Y154X pathogenic variant in the GJB1 gene, as the mutant allele was present but underrepresented in comparison to the normal allele. This result was confirmed using alternative, non-overlapping primers, making it unlikely that this result is due to uneven DNA amplification. Therefore, this pathogenic variant is interpreted to be present in some, but not all, cells in this peripheral blood specimen. Sanger sequencing is not a quantitative test; thus, it is not possible to determine more precisely the level of mosaicism in this specimen. The level of mosaicism may be different in other tissues.