Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
INGEBI, |
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) |