ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2785C>T (p.Arg929Ter) (rs1057516342)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000412338 SCV000485499 likely pathogenic Usher syndrome type 1F 2015-12-22 criteria provided, single submitter clinical testing
Invitae RCV000811416 SCV000951682 pathogenic not provided 2018-12-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg929*) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Usher syndrome (PMID: 25425308, 15660226, 25307757). ClinVar contains an entry for this variant (Variation ID: 370242). Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000412338 SCV001361472 likely pathogenic Usher syndrome type 1F 2019-03-07 criteria provided, single submitter clinical testing Variant summary: The variant, PCDH15 c.2785C>T (p.Arg929X) 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 been classified as pathogenic by our laboratory (eg.c.2971C>T/p.Arg991X). The variant allele was found at a frequency of 8.1e-06 in 245792 control chromosomes (gnomAD) and has been reported in the literature in individuals affected with Usher Syndrome Type 1 (Zein_2014, Ouyang_2005). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery,Institute of Otolaryngology, Chinese PLA General Hospital RCV000770852 SCV000902354 pathogenic Deafness, autosomal recessive 23 2019-02-26 no assertion criteria provided case-control

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