ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.148G>A (p.Asp50Asn) (rs28931594)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000412852 SCV000227306 pathogenic not provided 2014-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000412852 SCV000490534 pathogenic not provided 2015-06-16 criteria provided, single submitter clinical testing The D50N variant in the GJB2 gene is a common, recurrent pathogenic variant that accounts for the vast majority (>80%) of cases with keratitis-ichthyosis-deafness (KID) syndrome (Richard et al. 2002; van Steensel et al. 2002). As in this family, D50N occurs in most patients de novo, although autosomal dominant inheritance from an affected parent also has been documented (Richard et al., 2002; Mazereeuw-Hautier et al., 2007). In contrast, the D50N variant was never observed in approximately 6,500 unaffected control individuals of European and African American ancestry according to the NHLBI Exome Sequencing Project, further supporting its pathogenicity. The D50N variant results in a semi-conservative amino acid substitution of a residue in the first extracellular domain of connexin 26, which is a highly conserved region among all connexin genes across species, and a known mutational hotspot for autosomal dominant, syndromic GJB2 disorders. Functional studies have demonstrated that D50N disrupts normal connexin 26 hemichannel function (Lopez et al., 2013). In summary, we interpret D50N as a pathogenic variant.
OMIM RCV000018546 SCV000038828 pathogenic Keratitis-ichthyosis-deafness syndrome, autosomal dominant 2009-03-01 no assertion criteria provided literature only
OMIM RCV000018547 SCV000038829 pathogenic Hystrix-like ichthyosis with deafness 2009-03-01 no assertion criteria provided literature only
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000678868 SCV000805061 pathogenic Hearing loss 2006-10-17 no assertion criteria provided clinical testing

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