ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.4141del (p.Val1381fs) (rs778537772)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486224 SCV000574374 pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing The c.4141delG variant in the PKHD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.4141delG variant causes a frameshift starting with codon Valine 1381, changes this amino acid to a Cysteine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Val1381CysfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.4141delG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.4141delG as a pathogenic variant.
Invitae RCV000409248 SCV000629916 pathogenic Autosomal recessive polycystic kidney disease 2017-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1381Cysfs*7) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs778537772, ExAC 0.001%). This variant has not been reported in the literature in individuals with PKHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 371324). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000409248 SCV000486879 likely pathogenic Autosomal recessive polycystic kidney disease 2016-08-30 no assertion criteria provided clinical testing

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