ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.29T>C (p.Leu10Pro)

dbSNP: rs1959063711
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
INGEBI, INGEBI / CONICET 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)

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