ClinVar Miner

Submissions for variant NM_004004.6(GJB2):c.326G>T (p.Gly109Val)

dbSNP: rs374572413
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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 RCV001251625 SCV001427359 likely pathogenic Nonsyndromic genetic hearing loss 2020-08-04 criteria provided, single submitter clinical testing Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the c.326G>T, p.Gly109Val variant is absent from population databases (gnomAD, GO-ESP, 1000 genomes) meeting PM2 criteria. Computational evidence is not enoguh to meet neither PP3 nor BP4, since REVEL value is 0.534. This variant has been identified in trans with p.(Glu47*) mutation (PMID: 19051073) applying to PM3 criteria. Functional evidence demonstrated a significantly decrease of gap junction activity when p.Gly109Val mutant was tested (absence of currents through p.Gly109Val or WTCX26-G109V) in Xenopus laevis oocytes (PMID: 26769242) meeting PS3_Moderate criteria. Therefore, the c.326G>T variant meets criteria to be classified as likely pathogenic for autosomal recessive non-syndromic hearing loss (PM2, PM3 and PS3_Moderate)

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