ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2702A>C (p.Asn901Thr)

gnomAD frequency: 0.00001  dbSNP: rs764696718
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000700684 SCV000829450 pathogenic Autosomal recessive polycystic kidney disease 2024-01-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 901 of the PKHD1 protein (p.Asn901Thr). This variant is present in population databases (rs764696718, gnomAD 0.01%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 27225849, 30773290). 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: 577838). 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.
Laboratory of Molecular Diagnosis of Genetic Disease, Università degli Studi di Napoli Federico II RCV001507099 SCV001712070 likely pathogenic Caroli disease 2021-05-05 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001810482 SCV002060098 likely pathogenic Polycystic kidney disease 4 2021-11-08 criteria provided, single submitter clinical testing NM_138694.3(PKHD1):c.2702A>C(N901T) is a missense variant classified as likely pathogenic in the context of autosomal recessive polycystic kidney disease, PKHD1-related. N901T has been observed in cases with relevant disease (PMID: Raffaella_2017_(no PMID; thesis), 27225849, 30773290). Functional assessments of this variant are not available in the literature. N901T has been observed in population frequency databases (gnomAD: AMR 0.01%). In summary, NM_138694.3(PKHD1):c.2702A>C(N901T) is a missense variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
GeneDx RCV002469268 SCV002765528 likely pathogenic not provided 2022-12-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30773290, 34426522, 27225849, 35715958)
Baylor Genetics RCV001810482 SCV004204588 likely pathogenic Polycystic kidney disease 4 2023-08-09 criteria provided, single submitter clinical testing

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