ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.711_714del (p.Met238fs) (rs786204588)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725880 SCV000340221 pathogenic not provided 2016-03-24 criteria provided, single submitter clinical testing
Invitae RCV000169335 SCV000932569 pathogenic Autosomal recessive polycystic kidney disease 2019-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met238Serfs*7) 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 combination with another PKHD1 variant in several individuals affected with autosomal recessive polycystic kidney disease (PMID: 11898128, 19940839, 15805161). ClinVar contains an entry for this variant (Variation ID: 188960). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000169335 SCV001163077 pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000169335 SCV001364042 pathogenic Autosomal recessive polycystic kidney disease 2019-12-22 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.711_714delAATG (p.Met238SerfsX7) 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. The variant allele was found at a frequency of 8e-06 in 251376 control chromosomes. c.711_714delAATG has been reported in the literature in individuals affected with Polycystic Kidney and Hepatic Disease (example, Onuchic_2002, Denamur_2010 and Sharp_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. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Counsyl RCV000169335 SCV000220680 pathogenic Autosomal recessive polycystic kidney disease 2018-03-05 no assertion criteria provided clinical testing

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