ADGRV1, previously known as GPR98, was first reported in relation to autosomal recessive nonsyndromic hearing loss in 2013 (Yang et al., 23767834). At least 27 unique variants (missense, nonsense, frameshift, splice-site) have been reported in humans. Variants in this gene have been reported in at least 17 probands in 11 publications (23804846, 24123792, 23767834, 25528277, 25719458, 24853665, 29048421, 26226137, 26445815, 27068579, 28951997). Evidence disputing this gene-disease relationship includes lack of age information, lack of clinical examination history, and high allele frequency of variants in population databases. Of note, this gene has also been implicated in Usher syndrome Type 2. This has been assessed separately as Definitive. The mechanism of disease of ADGRV1-Usher syndrome Type 2 is homozygous loss of function, which is consistent with the variants reported in ADGRV1-nonsyndomic hearing loss patients. In summary, there is convincing evidence disputing the relationship between ADGRV1 and autosomal recessive nonsyndromic hearing loss. More evidence is needed to either support or refute the role ADGRV1 plays in this disease. This classification was approved by the ClinGen Hearing Loss Working Group on 3/19/19 (SOP Version 6).
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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