Submissions for variant NM_001384140.1(PCDH15):c.2581G>A (p.Val861Met)

gnomAD frequency: 0.00051  dbSNP: rs142512524

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000322580	SCV000363189	uncertain significance	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, 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000614926	SCV000711187	uncertain significance	not specified	2017-08-24	criteria provided, single submitter	clinical testing	The p.Val861Met variant in PCDH15 has been reported in the heterozygous state in one individual with Usher syndrome who did not carry a variant on the other all ele (Bujakowska 2014). It has also been identified in 0.09% (111/126546) of Euro pean chromosomes and 0.13% (46/34366) of Latino chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs142512524); th ough this frequency is not high enough to rule out a pathogenic role. Computatio nal prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of t he p.Val861Met variant is uncertain.
Fulgent Genetics, Fulgent Genetics	RCV000763656	SCV000894536	uncertain significance	Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001246481	SCV001419839	likely benign	not provided	2024-12-30	criteria provided, single submitter	clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375215	SCV001571917	uncertain significance	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	PM2_Supporting
Genome-Nilou Lab	RCV001578639	SCV001805901	uncertain significance	Autosomal recessive nonsyndromic hearing loss 23	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001578640	SCV001805902	uncertain significance	Usher syndrome type 1F	2021-07-14	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001246481	SCV001921524	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001246481	SCV001975540	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001578640	SCV002086643	uncertain significance	Usher syndrome type 1F	2020-01-19	no assertion criteria provided	clinical testing