Submissions for variant NM_001384140.1(PCDH15):c.2884C>T (p.Arg962Cys)

gnomAD frequency: 0.00039  dbSNP: rs201816080

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151628	SCV000199853	benign	not specified	2015-02-26	criteria provided, single submitter	clinical testing	p.Arg962Cys in exon 22 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 1.2% (101/8646) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs201816080). In addition, arginine (Arg) at position 962 is not well conserved across species and two variants (p.Arg962His and p.Arg962Leu) at the s ame position have been classified as benign or likely benign.
Illumina Laboratory Services, Illumina	RCV000343106	SCV000363175	likely benign	Usher syndrome type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000890106	SCV001033832	benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000988360	SCV001138048	benign	Usher syndrome type 1F	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000890106	SCV001771953	uncertain significance	not provided	2020-11-04	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26047050, 29625443, 30245029, 23967202, 31180159)
Natera, Inc.	RCV000988360	SCV001456426	likely benign	Usher syndrome type 1F	2020-04-23	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000890106	SCV001917096	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000890106	SCV001973866	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004734707	SCV005357914	likely benign	PCDH15-related disorder	2024-07-09	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).