ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.12200C>T (p.Pro4067Leu)

gnomAD frequency: 0.00003  dbSNP: rs758871283
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665449 SCV000789578 uncertain significance Autosomal recessive polycystic kidney disease 2017-02-14 criteria provided, single submitter clinical testing
GeneDx RCV001756122 SCV001985424 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing Identified prenatally in a patient with a clinical diagnosis of autosomal recessive polycystic kidney disease, including anhydramnios and enlarged kidneys, in published literature (Adeva et al., 2006); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16523049)
Invitae RCV000665449 SCV003330448 uncertain significance Autosomal recessive polycystic kidney disease 2023-12-21 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 4067 of the PKHD1 protein (p.Pro4067Leu). This variant is present in population databases (rs758871283, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of PKHD1-related conditions (PMID: 16523049). ClinVar contains an entry for this variant (Variation ID: 550648). 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 not expected to disrupt PKHD1 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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