The ILDR1 gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 10/20/2017. This association was made using case-level data and experimental data. At least 13 variants (missense, nonsense, frameshift, splice site) have been reported in humans. ILDR1 was first associated with this disease in humans as early as 2011 (Borck et al.). Association is seen in at least 15 probands in 4 publications (21255762, 23226338, 22903915, 27344577). Variants in this gene segregated with disease in more than 4 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and experimental evidence (18 pts.) has been reached. The mechanism for disease is biallelic LOF (21255762, 23226338, 22903915, 27344577, 25819842, 24990150). This gene-disease association is supported by mouse and zebrafish models as well as expression and protein interaction studies (21255762, 23239027, 25822906, 25819842, 24990150). In summary, ILDR1 is definitively associated with autosomal recessive nonsyndromic hearing loss. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Working Group on 11/21/2017.
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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