ClinVar Miner

Submissions for variant NM_138691.2(TMC1):c.1714G>A (p.Asp572Asn) (rs121908072)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000217542 SCV000271465 pathogenic Rare genetic deafness 2015-06-05 criteria provided, single submitter clinical testing The p.Asp572Asn in TMC1 has been previously reported in 3 probands with nonsyndr omic bilateral sensorineural hearing loss, and segregated with disease in a domi nant pattern in >10 affected family members (Kurima 2002, Hilgert 2009, Makishim a 2004, Wei 2014). The hearing loss was reported to be progressive with a postli ngual onset. The variant was identified in one unaffected individual from one fa mily, indicating that the penetrance may not be complete; however the age of thi s individual was also not reported (Hilgert 2009). This variant was absent from large population databases. A variant affecting the same amino acid (p.Asp572His ) has also been reported in an individual with hearing loss and segregated in 7 affected family members including 2 obligate carriers (Kitajiri 2007), further s upporting that missense variants at this position are not tolerated. Unlike loss of function variants in TMC1, which cause recessive hearing loss, these studies indicate that the p.Asp572Asn and p.Asp572His missense variants cause dominant hearing loss. In summary, the p.Asp572Asn variant meets our criteria to be class ified as pathogenic for autosomal dominant sensorineural hearing loss (http://ww w.partners.org/personalizedmedicine/LMM) based upon segregation studies in affec ted families and its absence in the general population.
Molecular Diagnostics Laboratory, M Health: University of Minnesota RCV000004318 SCV000891297 likely pathogenic Deafness, autosomal dominant 36 2016-09-28 criteria provided, single submitter clinical testing
OMIM RCV000004318 SCV000024489 pathogenic Deafness, autosomal dominant 36 2009-03-01 no assertion criteria provided literature only

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