ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.526_555dup (p.Thr176_Thr185dup)

dbSNP: rs1555937221
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480217 SCV000573064 likely pathogenic not provided 2017-02-17 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the GJB1 gene. The c.526_555dup30 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.526_555dup30 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server. The c.526_555dup30 variant results in an in-frame duplication of 10 amino acids denoted, p.Thr176_Thr185dup. Multiple missense variants in the duplicated region have been reported in the Human Gene Mutation Database in association with CMT1X (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000821391 SCV000962146 uncertain significance Charcot-Marie-Tooth Neuropathy X 2022-03-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 423372). This variant has not been reported in the literature in individuals affected with GJB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.526_555dup, results in the insertion of 10 amino acid(s) of the GJB1 protein (p.Thr176_Thr185dup), but otherwise preserves the integrity of the reading frame.

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