ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs754392766
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169415 SCV000220821 likely pathogenic Autosomal recessive polycystic kidney disease 2014-10-21 criteria provided, single submitter literature only
Eurofins Ntd Llc (ga) RCV000725681 SCV000338570 pathogenic not provided 2016-01-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Center for Personalized Medicine, Children's Hospital Los Angeles RCV000735398 SCV000854553 pathogenic Polycystic kidney disease criteria provided, single submitter clinical testing
Invitae RCV000169415 SCV000948795 pathogenic Autosomal recessive polycystic kidney disease 2024-01-11 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. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with clinical features of polycystic kidney disease (PMID: 15108281, 16523049, 19940839). ClinVar contains an entry for this variant (Variation ID: 189026). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000169415 SCV001163066 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002498843 SCV002805008 pathogenic Polycystic kidney disease 4 2022-03-15 criteria provided, single submitter clinical testing
Center for Personalized Medicine, Children's Hospital Los Angeles RCV003156078 SCV003845331 pathogenic See cases 2022-12-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV002498843 SCV004202273 pathogenic Polycystic kidney disease 4 2023-09-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV000169415 SCV002081077 pathogenic Autosomal recessive polycystic kidney disease 2020-11-12 no assertion criteria provided clinical testing

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