Submissions for variant NM_001384140.1(PCDH15):c.243G>A (p.Val81=)

gnomAD frequency: 0.00073  dbSNP: rs151119732

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039711	SCV000063400	likely benign	not specified	2017-02-28	criteria provided, single submitter	clinical testing	p.Val81Val in Exon 4 of PCDH15: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located ne ar a splice junction. It has also been identified in 0.1% (68/66706) European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; rs15119732).
Illumina Laboratory Services, Illumina	RCV000261127	SCV000363251	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587293	SCV000699757	likely benign	not provided	2016-09-26	criteria provided, single submitter	clinical testing	Variant summary: The PCDH15 c.243G>A (p.Val81Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 81/121286 control chromosomes at a frequency of 0.0006678, which does not exceed the estimated maximal expected allele frequency of a pathogenic PCDH15 variant (0.0031623). One clinical diagnostic laboratory has classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases. Taken together, this variant is classified as Likely Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000587293	SCV001038407	benign	not provided	2025-01-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000587293	SCV001944777	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587293	SCV005436339	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	PCDH15: BP4, BS2
Natera, Inc.	RCV001275407	SCV001460557	benign	Usher syndrome type 1F	2020-04-15	no assertion criteria provided	clinical testing