ClinVar

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with autosomal recessive non syndromic hearing loss. However dominant negative is a likely mechanism for missense variants (PMID: 28428247). (I) 0108 - This gene is associated with both recessive and dominant disease. Truncating variants most likely to result in lost protein function are more commonly reported for recessive disease, while missense are more commonly reported for dominant disease (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance. Two missense variants are most commonly reported with incomplete penetrance (PMID:31160754). (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with at least 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0305 - Variant is present in gnomAD v2 >=0.01 and <0.03 for a recessive condition (221 heterozygotes, 3 homozygotes). (I) 0701 - Other truncating variants downstream of the one identified in this case have very strong previous evidence for pathogenicity. Patients with these variants are generally reported with non syndromic autosomal recessive hearing loss (ClinVar, PMID: 26096904). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported many times as pathogenic, and has been reported in patients with autosomal recessive non syndromic hearing loss (ClinVar, PMID: 26096904) (SP) 1205 - This variant has been shown to be maternally inherited by trio analysis. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign