ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.324dup (p.Glu109Ter) (rs1555937143)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000598661 SCV000709918 likely pathogenic not provided 2018-03-06 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the GJB1 gene. The c.324dupT variant hasbeen reported previously in a family with X-linked Charcot-Marie-Tooth neuropathy; however,information regarding parental testing was not provided (Lee et al., 2002). The c.324dupT variantcauses a frameshift starting with codon Glutamic acid 109 and changes this amino acid to a premature Stop codon, denoted p.Glu109Ter. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 175 amino acids of the GJB1 protein are lost. Additionally, the c.324dupT variant is not observed in large population cohorts (Lek et al., 2016). Furthermore, other loss-of-function variants downstream of this position have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth neuropathy X, type 1 (CMTX1) (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Inherited Neuropathy Consortium RCV000789256 SCV000928608 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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