Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
INGEBI, |
RCV001257046 | SCV001433597 | uncertain significance | Nonsyndromic genetic hearing loss | 2020-08-31 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the filtering allele frequency of the c.29T>C, p.Leu10Pro variant in GJB2 gene is absent from population database gnomAD, GO-ESP, 1000 genomes) meeting PM2 criteria. This variant has been identified twice in heterozygous state and with p.Val27Ile benign variant in unknown phase in patients with hearing loss (PMID: 19887791, 12865758). Computational evidence suggested a damage impact of the mutation to the protein applying to PP3 criteria (REVELscore: 0.936). Functional studies in Hela Cells and Xenopus Laevis oocytes demonstrated difference voltage dependence and solute permeability properties in p.Leu10Pro mutant compared to WT-CX26 meeting PS3_Moderate rule (PMID: 26769242). In summary, the clinical significance of this variant is currently uncertain (PM2, PP3, PS3_Moderate) |