Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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 | |
Gene |
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, |
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, |
RCV000490112 | SCV001448748 | pathogenic | not provided | 2019-03-22 | criteria provided, single submitter | clinical testing | |
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 | |
Ce |
RCV000490112 | SCV004010216 | pathogenic | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing | GJB2: PM3:Very Strong, PM2, PP1, PP3 |
Natera, |
RCV000037855 | SCV002086069 | pathogenic | Autosomal recessive nonsyndromic hearing loss 1A | 2020-10-16 | no assertion criteria provided | clinical testing |