ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.44A>C (p.Lys15Thr)

gnomAD frequency: 0.00003  dbSNP: rs111033217
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000211780 SCV000061517 pathogenic Rare genetic deafness 2020-10-14 criteria provided, single submitter clinical testing The p.Lys15Thr variant in GJB2 has been reported in the compound heterozygous state with another pathogenic variant in GJB2 in at least 6 individuals with hearing loss, and segregated in 5 affected relatives of three families (Wu 2002 PMID: 12172394, Lim 2003 PMID: 12925341, Welch 2007 PMID: 17431919, LMM data). This variant has been identified in 3/111888 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs111033217); this frequency is low enough to be consistent with a recessive carrier frequency for recessive hearing loss. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive nonsyndromic hearing. ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PM2_Supporting.
Counsyl RCV000037855 SCV000220863 likely pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2014-11-07 criteria provided, single submitter literature only
GeneDx RCV000490112 SCV000577003 likely pathogenic not provided 2024-02-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31970404, 12172394, 26778469, 21465647, 17666888, 12925341, 12865758, 16154643, 16950989, 27340645, 25388846, 16380907, 12910486, 19235794, 15253766, 31160754, 19775242, 17431919, 36515421)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000037855 SCV000599724 likely pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2017-05-09 criteria provided, single submitter clinical testing
Invitae RCV000490112 SCV001393336 pathogenic not provided 2023-09-15 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 15 of the GJB2 protein (p.Lys15Thr). This variant is present in population databases (rs111033217, gnomAD 0.002%). This missense change has been observed in individual(s) with non-syndromic deafness (PMID: 12172394, 15253766, 17431919). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 44752). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GJB2 protein function. For these reasons, this variant has been classified as Pathogenic.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000490112 SCV001448748 pathogenic not provided 2019-03-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002490513 SCV002811622 pathogenic Autosomal recessive nonsyndromic hearing loss 1A; Mutilating keratoderma; Ichthyosis, hystrix-like, with hearing loss; Autosomal dominant keratitis-ichthyosis-hearing loss syndrome; Palmoplantar keratoderma-deafness syndrome; Knuckle pads, deafness AND leukonychia syndrome; Autosomal dominant nonsyndromic hearing loss 3A; X-linked mixed hearing loss with perilymphatic gusher 2021-12-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000490112 SCV004010216 pathogenic not provided 2023-06-01 criteria provided, single submitter clinical testing GJB2: PM3:Very Strong, PM2, PP1, PP3
Natera, Inc. RCV000037855 SCV002086069 pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2020-10-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.