The TMPRSS3 gene has been associated with autosomal recessive nonsyndromic hearing loss using the ClinGen Clinical Validity Framework as of 8/16/2016. This association was made using case-level data only. At least 8 missense, frameshift, and splice-site variants have been reported in humans. TMPRSS3 was first associated with this disease in humans as early as 2001 (Scott et al.). Association is seen in at least 9 probands in 5 publications (11137999, 28695016, 25474651, 26036852, 11907649). Variants in this gene segregated with disease in multiple additional family members. More evidence is available in the literature, but the maximum score for genetic evidence and/or experimental evidence (12 pts.) has been reached. This gene-disease association is supported by a mouse model, expression studies, and functional assays. In summary, TMPRSS3 is definitively associated with autosomal recessive nonsyndromic hearing loss. This classification was approved by the ClinGen Hearing Loss Working Group on 8/22/2017.
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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