ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.11314C>T (p.Arg3772Ter) (rs199839578)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411765 SCV000485553 likely pathogenic Autosomal recessive polycystic kidney disease 2016-01-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000411765 SCV000699844 pathogenic Autosomal recessive polycystic kidney disease 2017-05-29 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.11314C>T (p.Arg3772X) 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 likely pathogenic in ClinVar (e.g. p.Arg3842Ter and c.11776delG (p.Val3926Trpfs)). This variant is absent in 121176 control chromosomes from ExAC. This variant has been reported in five patients from four ARPKD families (Bergmann_2004, Melchionda_2016; Li_2016), in homozygous state and in compound heterozygous state with known, c.9689delA (p.Asp3230fs) and presumably pathogenic, c.889T>A (p.Cys297Ser) variants. Parents were genotyped in both families and variant transmission in affected offspring's was consistent with disease inheritance. One clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000411765 SCV000956252 pathogenic Autosomal recessive polycystic kidney disease 2019-05-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg3772*) 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 individuals affected with polycystic kidney disease (PMID: 15108281, 27225849, 27577217). ClinVar contains an entry for this variant (Variation ID: 370289). 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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