Submissions for variant NM_033056.4(PCDH15):c.4907_4908del (p.Lys1636fs)

dbSNP: rs1491209806

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667172	SCV000791581	uncertain significance	Usher syndrome type 1F	2017-05-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001238927	SCV001411763	likely benign	not provided	2024-02-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001238927	SCV002586773	uncertain significance	not provided	2022-04-15	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 320 amino acids are replaced with 6 different amino acids, and other loss-of-function variants have been reported downstream in HGMD.; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002307583	SCV002600419	uncertain significance	not specified	2022-10-10	criteria provided, single submitter	clinical testing	Variant summary: PCDH15 c.4907_4908delAA (p.Lys1636ArgfsX7) located in the last exon of the gene results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay. Truncating variants in the last exon of PCDH15 have uncertain impact on protein function. The variant allele was found at a frequency of 4.8e-05 in 251448 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in PCDH15 causing Usher Syndrome Type 1F (4.8e-05 vs 0.0032), allowing no conclusion about variant significance. c.4907_4908delAA has been reported in the literature in one individual in a carrier screening (Perreault_2014). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome Type 1F. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002499158	SCV002797612	uncertain significance	Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F	2021-08-02	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000667172	SCV002089034	uncertain significance	Usher syndrome type 1F	2020-01-10	no assertion criteria provided	clinical testing