ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1480C>T (p.Arg494Ter) (rs754392766)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735398 SCV000854553 pathogenic Polycystic kidney dysplasia criteria provided, single submitter clinical testing
Counsyl RCV000169415 SCV000220821 likely pathogenic Autosomal recessive polycystic kidney disease 2014-10-21 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725681 SCV000338570 pathogenic not provided 2016-01-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000169415 SCV000699849 pathogenic Autosomal recessive polycystic kidney disease 2017-01-26 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.1480C>T (p.Arg494X) variant results in a premature termination codon, predicted to cause a truncated or absent PKHD1 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.c.1486C>T/p.Arg496X, c.3761_3762delinsG/p.Ala1254fsX49). One in silico tool predicts a damaging outcome for this variant. This variant has been reported in at least three ARPKD patients and is absent in 121400 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000169415 SCV000948795 pathogenic Autosomal recessive polycystic kidney disease 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg494*) in the PKHD1 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 multiple individuals with clinical features of polycystic kidney disease (PMID: 16523049, 19940839, 15108281). ClinVar contains an entry for this variant (Variation ID: 189026). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.

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