Submissions for variant NM_000166.6(GJB1):c.124_125del (p.Ser42fs)

dbSNP: rs1602348794

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000799767	SCV000939445	pathogenic	Charcot-Marie-Tooth Neuropathy X	2021-09-19	criteria provided, single submitter	clinical testing	This variant is also known as p.Ser42CysfsX45. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB1 protein in which other variant(s) (p.Tyr65*) have been determined to be pathogenic (PMID: 22464564). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with X-linked Charcot-Marie-Tooth disease type 1X (PMID: 22464564). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser42Cysfs*4) in the GJB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 242 amino acid(s) of the GJB1 protein.
Inherited Neuropathy Consortium	RCV000789808	SCV000929192	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only
Inherited Neuropathy Consortium Ii, University Of Miami	RCV003447274	SCV004174689	uncertain significance	Charcot-Marie-Tooth disease X-linked dominant 1	2016-01-06	no assertion criteria provided	literature only