ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.133G>A (p.Gly45Arg) (rs1326514987)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672597 SCV000797712 uncertain significance Deafness, autosomal recessive 1A 2018-02-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825343 SCV000966638 uncertain significance not specified 2018-07-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly45Arg variant in GJB2 has been reported in 1 individual with non-syndromic hearing los s (Rodriguez-Paris 2016). In addition, in vitro fluorescence microscopy studies suggest impaired permeability of IP3 through the connexin-26 (GJB2) channel for the p.Gly45Arg variant, potentially in an autosomal dominant manner (Rodriguez-P aris 2016). This variant has also been identified in 1/8722 of African chromosom es by the Genome Aggregation Database (gnomAD, . Computational prediction tools and conservation analysis suggest that the p.Gl y45Arg variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion fo r a pathogenic role, the clinical significance of the p.Gly45Arg variant is unce rtain. ACMG/AMP Criteria applied: PM2; PP3; PS3_Supporting.

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