The relationship between CLDN14 and autosomal recessive nonsyndromic hearing loss was evaluated using the ClinGen Clinical Validity Framework as of 11/17/2017. Variants in CLDN14 were first reported in humans with this disease as early as 2001 (Wilcox et al.). At least 7 variants (e.g. missense, in-frame indel, nonsense, frameshift) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and experimental data. Variants in this gene have been reported in at least 12 probands in 6 publications (11163249, 20811388, 22246673, 23235333, 27870113, 27838790). Variants in this gene segregated with disease in at least 49 additional family members. Many of the reported variants are believed to be founder variants from Pakistan and Newfoundland and Labrador Province. This gene-disease association is supported by a knockout mouse model and additional expression and functional alteration evidence. In summary, CLDN14 is definitively associated with autosomal recessive nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 5/1/2018.
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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