ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10350C>A (p.Cys3450Ter) (rs765652131)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781723 SCV000919991 likely pathogenic Autosomal recessive polycystic kidney disease 2017-12-11 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.10350C>A (p.Cys3450X) 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.10637delT, p.Val3546fsX22; c.11314C>T, p.Arg3772X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 245638 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000781723 SCV001216302 pathogenic Autosomal recessive polycystic kidney disease 2019-04-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys3450*) 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 not been reported in the literature in individuals with PKHD1-related conditions. 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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