ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.467T>G (p.Leu156Arg) (rs104894818)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256065 SCV000322234 pathogenic not provided 2020-07-14 criteria provided, single submitter clinical testing Reported in families with X-linked Charcot-Marie-Tooth disease in published literature (Bergoffen et at., 1993; Bone et al., 1995); Published functional studies demonstrate that L156R mutant formed defective junctional channels (Wang et al., 2004); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 15006706, 9361298, 7477983, 26955336, 8266101)
Invitae RCV000463876 SCV000544773 likely pathogenic Charcot-Marie-Tooth Neuropathy X 2020-03-18 criteria provided, single submitter clinical testing This sequence change replaces leucine with arginine at codon 156 of the GJB1 protein (p.Leu156Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with Charcot-Marie-Tooth disease (PMID: 7477983, 8266101, 9018031, 17353473, 26955336). ClinVar contains an entry for this variant (Variation ID: 10437). Experimental studies have shown that this missense change adversely affects protein function (PMID: 15006706). In summary, this variant is a rare missense change that has been reported in affected individuals and has been shown to affect protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Athena Diagnostics Inc RCV000256065 SCV000841717 pathogenic not provided 2017-12-29 criteria provided, single submitter clinical testing
OMIM RCV000011182 SCV000031409 pathogenic Charcot-Marie-Tooth Neuropathy X Type 1 1995-10-01 no assertion criteria provided literature only

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