ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.266T>C (p.Leu89Pro) (rs1555937122)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000516283 SCV000613481 pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing
Invitae RCV000552811 SCV000658905 pathogenic Charcot-Marie-Tooth Neuropathy X 2017-02-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 89 of the GJB1 protein (p.Leu89Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with CMTX1 (PMID: 26274329, 12457340, 9099841) and it has been reported to segregate with disease in a family affected with X-linked dominant Charcot-Marie-Tooth disease (CMTX1) (PMID: 17714866). This variant is also known as leu238pro in the literature. Experimental studies have found that this missense change impacts the cellular localization of the GJB1-encoded CX32 protein, preventing the formation of functional CX32 gap junctions (PMID: 27367520). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789233 SCV000928585 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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