ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9662C>T (p.Pro3221Leu)

gnomAD frequency: 0.00016  dbSNP: rs145141656
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000729058 SCV000856694 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000729058 SCV001154767 uncertain significance not provided 2017-06-01 criteria provided, single submitter clinical testing
Invitae RCV001239749 SCV001412646 likely pathogenic Autosomal recessive polycystic kidney disease 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 3221 of the PKHD1 protein (p.Pro3221Leu). This variant is present in population databases (rs145141656, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of polycystic kidney disease (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 593890). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV000729058 SCV001989600 uncertain significance not provided 2023-07-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002485863 SCV002776687 uncertain significance Polycystic kidney disease 4 2022-04-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV004026962 SCV005005335 uncertain significance Inborn genetic diseases 2021-06-22 criteria provided, single submitter clinical testing The c.9662C>T (p.P3221L) alteration is located in exon 58 (coding exon 57) of the PKHD1 gene. This alteration results from a C to T substitution at nucleotide position 9662, causing the proline (P) at amino acid position 3221 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001239749 SCV002077940 uncertain significance Autosomal recessive polycystic kidney disease 2018-05-03 no assertion criteria provided clinical testing

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