ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.282C>A (p.His94Gln) (rs756000896)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236380 SCV000292796 pathogenic not provided 2015-04-22 criteria provided, single submitter clinical testing The H94Q missense variant in the GJB1 gene has been reported previously in association with Charcot-Marie-Tooth disease, and functional studies in Xenopus oocytes have shown that H94Q alters channel properties (Abrams et al., 2001; Bone et al., 1997; Fiorentino et al., 2006). A different nucleotide substitution at the same position (c.282 C>G) resulting in the same amino acid change (H94Q), as well as different missense substitutions at the same position (H94R/Y/D), have also been reported (Abrams et al., 2001; Arthur-Farraj et al., 2012; Bone et al., 1997; Dubourg et al., 2001; IPNMDB database). Additionally, other missense variants in nearby residues (M93R/K/V; V95M) have also been reported in association with CMT (Stenson et al., 2014). The H94Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts H94Q is probably damaging to the protein structure/function. The presence of this pathogenic variant in the GJB1 gene is consistent with a diagnosis of Charcot-Marie-Tooth neuropathy X, type 1 (CMTX1)
Inherited Neuropathy Consortium RCV000789853 SCV000929238 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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