Submissions for variant NM_001384140.1(PCDH15):c.2563C>T (p.Arg855Trp)

gnomAD frequency: 0.00121  dbSNP: rs138010738

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039712	SCV000063401	likely benign	not specified	2016-06-16	criteria provided, single submitter	clinical testing	p.Arg855Trp in exon 20 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.3% (34/10400) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs138010738).
Illumina Laboratory Services, Illumina	RCV000259703	SCV000363191	uncertain significance	Usher syndrome type 1	2018-01-13	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000658086	SCV000779857	uncertain significance	not provided	2024-09-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15537665)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000658086	SCV001041960	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658086	SCV005892566	uncertain significance	not provided	2025-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001273393	SCV001456427	uncertain significance	Usher syndrome type 1F	2020-01-07	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000658086	SCV001979354	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000658086	SCV001980130	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541127	SCV004784362	likely benign	PCDH15-related disorder	2022-10-26	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).