Submissions for variant NM_033056.4(PCDH15):c.5435C>T (p.Pro1812Leu)

gnomAD frequency: 0.00013  dbSNP: rs139668636

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000216469	SCV000269628	benign	not specified	2015-05-07	criteria provided, single submitter	clinical testing	p.Pro1812Leu in exon 33 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 5.3% (11/208) of Japanese chromo somes by the 1000 Genomes Project and 0.3% (19/7292) of East Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs139668636).
Eurofins Ntd Llc (ga)	RCV000724949	SCV000332669	uncertain significance	not provided	2015-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000724949	SCV000620031	uncertain significance	not provided	2021-06-02	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724949	SCV001052023	likely benign	not provided	2025-01-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001105922	SCV001262937	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.
PreventionGenetics, part of Exact Sciences	RCV004530281	SCV004752894	likely benign	PCDH15-related disorder	2022-12-23	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).