ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.737T>C (p.Ile246Thr)

dbSNP: rs1037991711
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667175 SCV000791588 uncertain significance Autosomal recessive polycystic kidney disease 2017-05-12 criteria provided, single submitter clinical testing
Invitae RCV000667175 SCV001403134 pathogenic Autosomal recessive polycystic kidney disease 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 246 of the PKHD1 protein (p.Ile246Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 19914852, 24162162). 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: 551992). 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 80%. For these reasons, this variant has been classified as Pathogenic.

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