ClinVar Miner

Submissions for variant NM_138691.2(TMC1):c.236+1G>A (rs775428246)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000770875 SCV000924178 pathogenic Deafness, autosomal recessive 7 criteria provided, single submitter research
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770875 SCV000902389 pathogenic Deafness, autosomal recessive 7 2019-02-26 no assertion criteria provided case-control
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000626300 SCV000746961 likely pathogenic Deafness, autosomal dominant 36 2017-12-18 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000608719 SCV000711267 pathogenic Rare genetic deafness 2016-05-27 criteria provided, single submitter clinical testing The c.236+1G>A variant in TMC1 has been reported in 2 homozygous individuals wit h autosomal recessive nonsyndromic sensorineural hearing loss and segregated wit h hearing loss in 4 affected relatives from those 2 families (Hilgert 2008, Hild ebrand 2010). Another variant at the same position c.236+1G>C has also been repo rted as pathogenic in the literature (Yang 2013). This variant has been identifi ed in 1/42270 European chromosomes by the Exome Aggregation Consortium (ExAC, ht tp://exac.broadinstitute.org; dbSNP rs775428246). Although this variant has been seen in the general population, its frequency is low enough to be consistent wi th a recessive carrier frequency. This variant occurs in the invariant region (+ /- 1/2) of the splice consensus sequence and is predicted to cause altered splic ing leading to an abnormal or absent protein. Loss of function of the TMC1 gene is an established disease mechanism in autosomal recessive nonsyndromic sensorin eural hearing loss. In summary, this variant meets our criteria to be classified as pathogenic for autosomal recessive nonsyndromic sensorineural hearing loss.

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