The relationship between ATP6V1B1 and autosomal recessive renal tubular acidosis with deafness was evaluated using the ClinGen Clinical Validity Framework as of 12/13/2017. Variants in ATP6V1B1 were first reported in humans with this disease as early as 1999 (Karet et al.). At least 6 variants (missense, nonsense, frameshift) have been reported in humans. Many more papers have been published since the original Kerat et al. 1999 paper with autosomal recessive renal tubular acidosis and hearing loss cases due to ATP6V1B1 variants, however the maximum score for genetic evidence has been reached. The majority of patients have LOF variants, with some missense cases. There is one mouse model with a homozygous missense ATP6V1B1 variant resulting in hearing loss, however there is a knockout model in which the mice have renal tubular acidosis and normal hearing (PMID 28934385, 12782355). Hearing loss prevalence is about 90%. In summary, ATP6V1B1 is definitively associated with autosomal recessive renal tubular acidosis with deafness. This classification was approved by the ClinGen Hearing Loss Working Group on 12/19/2017.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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