ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1978T>C (p.Cys660Arg)

dbSNP: rs727504092
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001379301 SCV001577076 pathogenic Autosomal recessive polycystic kidney disease 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 660 of the PKHD1 protein (p.Cys660Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 33940108; 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: 167494). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000153723 SCV004034337 likely pathogenic not provided 2024-05-03 criteria provided, single submitter clinical testing Reported with a second variant (phase unknown) in a patient with polycystic kidney disease in published literature (PMID: 33940108); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33940108)
Eurofins Ntd Llc (ga) RCV000153723 SCV000203281 uncertain significance not provided 2015-10-27 flagged submission clinical testing

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