ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.564_565del (p.Lys188fs)

dbSNP: rs770116143
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409267 SCV000487446 likely pathogenic Autosomal recessive nonsyndromic hearing loss 1A 2016-09-09 criteria provided, single submitter clinical testing
Counsyl RCV000410369 SCV000487447 likely pathogenic Autosomal dominant nonsyndromic hearing loss 3A 2016-09-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000602023 SCV000712531 pathogenic Rare genetic deafness 2016-10-25 criteria provided, single submitter clinical testing The p.Lys188fs variant in GJB2 has been reported in 1 individual with hearing lo ss (Azaiez 2004). This variant has been identified in 2/10270 African chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs770116143); however, this frequency is low enough to be consistent with a r ecessive carrier frequency. This variant is predicted to cause a frameshift, whi ch alters the protein?s amino acid sequence beginning at position 188 and leads to a premature termination codon 21 amino acids downstream. In summary, this var iant is pathogenic for autosomal recessive hearing loss based on its predicted i mpact on the protein.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003114528 SCV003799770 pathogenic not provided 2022-07-08 criteria provided, single submitter clinical testing The GJB2 c.564_565delGA; p.Lys188AsnfsTer21 variant (rs770116143) is reported in the literature in an individual with hearing loss (Azaiez 2004). This variant is also reported in ClinVar (Variation ID: 371691). It is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting two nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Azaiez H et al. GJB2: the spectrum of deafness-causing allele variants and their phenotype. Hum Mutat. 2004 Oct;24(4):305-11. PMID: 15365987.
Mayo Clinic Laboratories, Mayo Clinic RCV003114528 SCV005414133 likely pathogenic not provided 2024-07-30 criteria provided, single submitter clinical testing PM2_moderate, PVS1_strong

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