ClinVar Miner

Submissions for variant NM_004086.3(COCH):c.151C>T (p.Pro51Ser) (rs28938175)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000211754 SCV000840518 pathogenic Nonsyndromic hearing loss and deafness 2018-09-19 reviewed by expert panel curation The c.151C>T (p.Pro51Ser) variant in COCH has been reported to segregate with late onset progressive hearing loss and vestibular dysfunction in > 25 family members (PP1_S; PMID: 9931344, 11332404). The variant meets PM2 and has been observed in at least 15 affected probands (PS4, PMID: 28733840, 16151338, 11332404). The allele frequency of the p.Pro51Ser variant is 0.001% (1/111716) of European chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), which is a low enough frequency to award PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss (PM2). Computational prediction tools and conservation analysis suggest that the p.Pro51Ser variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PP1_S, PS4, PM2, PP3.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844626 SCV000061537 pathogenic Rare genetic deafness 2011-11-14 criteria provided, single submitter clinical testing The Pro51Ser variant in COCH has segregated in many Dutch families with late ons et autosomal dominant progressive sensorineural hearing loss with vestibular def ects (Bischoff 2005, de Kok 1999, Fransen 2001). It has been suggested that this variant is likely a found mutation in the Dutch population. In summary, this va riant meets our criteria to be classified as pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001093033 SCV001249825 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375055 SCV001571769 likely pathogenic Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PS1_Strong, PM2_Moderate, PP3_Supporting
OMIM RCV000006990 SCV000027186 pathogenic Deafness, autosomal dominant 9 2009-02-01 no assertion criteria provided literature only
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001093033 SCV001808054 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001093033 SCV001968774 pathogenic not provided no assertion criteria provided clinical testing

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