Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150744 | SCV000198184 | likely benign | not specified | 2015-02-27 | criteria provided, single submitter | clinical testing | p.Leu218_Asp221del in exon 2 of GJB3: This variant is not expected to have clini cal significance because the region affected by this 4 amino acid in-frame delet ion is poorly conserved across mammals and evolutionarily distant species. In ad dition, in a family with erythrokeratodermia variabalis (EKV) without hearing lo ss, this variant was detected in both affected and unaffected family members, wh ile a variant that arose de novo on the same allele (in cis) in one individual s egregated with disease in her children, indicating that the de novo variant is c ausative for the EKV, and the p.Leu218_Asp221del is unrelated to the disease (Ri chard 2000). This variant has also been identified in 2/8250 European American c hromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/E VS/). |
Eurofins Ntd Llc |
RCV000724547 | SCV000227516 | uncertain significance | not provided | 2015-01-22 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000724547 | SCV000885522 | likely benign | not provided | 2017-12-29 | criteria provided, single submitter | clinical testing | The GJB3 p.Leu218_Asp221del variant (rs727503069) has not been reported in association with hearing loss or deafness, but it has been identified in a family with erythrokeratodermia variabilis without hearing loss; however, this variant was identified in both affected and unaffected individuals whereas another variant that was on the same allele (in cis) and arose de novo in one individual was found only in affected family members (Richard 2000). Collectively, these observations suggest that the p.Leu218_Asp221del is not responsible for disease. Furthermore, the four amino acids that are removed by this in-frame deletion are poorly conserved (UCSC). The p.Leu218_Asp221del variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.14% in the Ashkenazi Jewish population (identified in 14 out of 10,148 chromosomes), and is found in the ClinVar database (Variant ID: 163536). Based on the available evidence, the p.Leu218_Asp221del variant is classified as likely benign. |
Ce |
RCV000724547 | SCV001147226 | likely benign | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000724547 | SCV001831915 | likely benign | not provided | 2021-05-14 | criteria provided, single submitter | clinical testing | Observed in both affected and unaffected individuals in a family with erythrokeratodermia variabilis in published literature; affected patients also harbored a de novo variant on the same allele (in cis) (Richard et al., 2000); In-frame deletion of 4 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 10798362) |
Invitae | RCV000724547 | SCV002144433 | uncertain significance | not provided | 2023-12-15 | criteria provided, single submitter | clinical testing | This variant, c.652_663del, results in the deletion of 4 amino acid(s) of the GJB3 protein (p.Leu218_Asp221del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768372993, gnomAD 0.1%). This variant has been observed in individual(s) with clinical features of autosomal dominant erythrokeratodermia variabilis (PMID: 10798362). This variant is also known as 652del12, ∆LHKD218-221. ClinVar contains an entry for this variant (Variation ID: 163536). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |