Submissions for variant NM_001384140.1(PCDH15):c.3795A>T (p.Glu1265Asp)

gnomAD frequency: 0.01533  dbSNP: rs111033496

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039733	SCV000063422	benign	not specified	2011-09-17	criteria provided, single submitter	clinical testing	Glu1265Asp in exon 28 of PCDH15: Glutamate at position 2072 is not conserved acr oss species (3 other amino acids at this position across 14 species) and the Asp artate variant is present in chicken and frog, suggesting that variation at this position is tolerated and unlikely to disrupt protein function. In addition, th is variant is predicted to be benign by three computational programs (AlignGVGD, SIFT, PolyPhen2). In summary, this variant is likely benign.
Illumina Laboratory Services, Illumina	RCV000347883	SCV000363155	benign	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000039733	SCV000514046	benign	not specified	2016-10-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000956825	SCV001103612	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000956825	SCV005322673	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001274790	SCV001459215	benign	Usher syndrome type 1F	2020-09-16	no assertion criteria provided	clinical testing