Submissions for variant NM_004004.6(GJB2):c.560_605dup (p.Cys202Ter)

dbSNP: rs1566528185

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001040588	SCV001204171	pathogenic	not provided	2023-08-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB2 protein in which other variant(s) (p.Leu213*, p.Cys211*) have been determined to be pathogenic (PMID: 15150777, 23141775). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 627447). This premature translational stop signal has been observed in individual(s) with autosomal recessive nonsyndromic deafness (PMID: 23141775). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys202*) in the GJB2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the GJB2 protein.
3billion, Medical Genetics	RCV001809798	SCV002059140	likely pathogenic	Autosomal dominant nonsyndromic hearing loss 3A	2022-01-03	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_S). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 23141775, PM3_M). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). The variant has been reported to co-segregate with the disease in at least one similarly affected relative/individual in the same family or similarly affected unrelated family (PMID: 23141775, PP1_P).Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796300	SCV005417468	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		criteria provided, single submitter	clinical testing	PVS1+PM2_Supporting+PM3_Strong
Fulgent Genetics, Fulgent Genetics	RCV004796300	SCV005632539	likely 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	2024-01-11	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000770823	SCV000902321	pathogenic	Autosomal recessive nonsyndromic hearing loss 1A	2019-02-26	no assertion criteria provided	case-control