ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.5721_5724del (p.Leu1908fs)

dbSNP: rs568470164
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001537421 SCV001754305 uncertain significance not provided 2024-12-18 criteria provided, single submitter clinical testing Reported in a patient undergoing carrier screening in published literature, however, case-level information was not provided (PMID: 25307757); Frameshift variant predicted to result in abnormal protein length as the last 48 amino acids are replaced with 14 different amino acids, and other similar variants have been reported in HGMD; This variant is associated with the following publications: (PMID: 33090715, 25307757)
Labcorp Genetics (formerly Invitae), Labcorp RCV001537421 SCV003255269 likely benign not provided 2025-01-23 criteria provided, single submitter clinical testing
Natera, Inc. RCV001832732 SCV002080141 uncertain significance Usher syndrome type 1F 2020-06-10 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004734225 SCV005345689 uncertain significance PCDH15-related disorder 2024-08-29 no assertion criteria provided clinical testing The PCDH15 c.5721_5724delTCTA variant is predicted to result in a frameshift and premature protein termination (p.Leu1908Alafs*15). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0099% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant occurs in the last exon of the PCDH15 alternatively spliced transcript known as CD1 (NM_033056), but this exon is not required for proper inner ear hair cell function and maintenance of hearing and is not included in the biologically relevant transcript for hearing loss known as CD2 (NM_001142769; Webb et al. 2011. PubMed ID: 21427143; Pepermans et al. 2014. PubMed ID: 24940003). Furthermore, loss of function variants in this exon of CD1 have been shown to occur at population frequencies inconsistent with pathogenicity (Perreault-Micale et al. 2014. PubMed ID: 25307757). This variant is interpreted as suspected benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.