Submissions for variant NM_033056.4(PCDH15):c.5682dup (p.Ser1895fs)

dbSNP: rs1287068204

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000671545	SCV000796530	uncertain significance	Usher syndrome type 1F	2017-12-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000671545	SCV001983680	likely pathogenic	Usher syndrome type 1F	2021-09-21	criteria provided, single submitter	clinical testing	Variant summary: PCDH15 c.5682dupA (p.Ser1895IlefsX4) 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, which are commonly known mechanisms for disease. Truncations downstream of this position have not been classified as pathogenic by our laboratory. However, several truncations downstream of this position (example, c.5847_5848delCA, c.5721_5724delTCTA, c.5717dupA) have been reported in association with phenotypes of Retinitis pigmentosa and cone rod dystrophy in the HGMD database. The variant was absent in 251372 control chromosomes. To our knowledge, no occurrence of c.5682dupA in individuals affected with Usher Syndrome Type 1F and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.