ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.1737C>G (p.Tyr579Ter) (rs1057517251)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410287 SCV000486983 likely pathogenic Usher syndrome type 1F 2016-09-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000410287 SCV000917969 likely pathogenic Usher syndrome type 1F 2018-06-11 criteria provided, single submitter clinical testing Variant summary: PCDH15 c.1737C>G (p.Tyr579X) 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 (e.g., p.Arg991X). The variant allele was found at a frequency of 4.1e-06 in 245806 control chromosomes, which does not exceed the maximal expected allele frequency for a pathogenic variant in PCDH15. c.1737C>G has been reported in the literature in individuals affected with Usher Syndrome Type 1F (Jaijo_2012, Kletke_2017). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001050534 SCV001214649 pathogenic not provided 2019-12-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr579*) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs1057517251, ExAC 0.009%). This variant has been observed in individuals affected with Usher syndrome (PMID: 22815625, 27743452, 30459346). This variant is also known as Tyr584X in the literature. ClinVar contains an entry for this variant (Variation ID: 371411). 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.
Blueprint Genetics RCV001073718 SCV001239277 pathogenic Retinal dystrophy 2017-07-26 criteria provided, single submitter clinical testing

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