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

dbSNP: rs28938175

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Hearing Loss Variant Curation Expert Panel	RCV000211754	SCV000840518	pathogenic	Nonsyndromic genetic hearing loss	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, Mass General Brigham 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 Center for Human Genetics 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	Autosomal dominant nonsyndromic hearing loss 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