ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.3467C>T (p.Ser1156Leu)

gnomAD frequency: 0.00004  dbSNP: rs367707903
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788447 SCV000927563 likely pathogenic not provided 2018-03-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV001004206 SCV001163051 likely pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Invitae RCV001004206 SCV001198042 pathogenic Autosomal recessive polycystic kidney disease 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1156 of the PKHD1 protein (p.Ser1156Leu). This variant is present in population databases (rs367707903, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 16199545, 20413436, 27225849, 33437033). 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: 636580). 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%. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research RCV000788447 SCV001422382 likely pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001810487 SCV002060093 likely pathogenic Polycystic kidney disease 4 2021-11-01 criteria provided, single submitter clinical testing NM_138694.3(PKHD1):c.3467C>T(S1156L) is a missense variant classified as likely pathogenic in the context of autosomal recessive polycystic kidney disease, PKHD1-related. S1156L has been observed in cases with relevant disease (PMID: 27225849, 27752906, 15698423, 19914852, 33940108, 33426401). Functional assessments of this variant are not available in the literature. S1156L has been observed in population frequency databases (gnomAD: NFE 0.01%). In summary, NM_138694.3(PKHD1):c.3467C>T(S1156L) 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.
Mendelics RCV001810487 SCV002518868 pathogenic Polycystic kidney disease 4 2022-05-04 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001810487 SCV002798983 likely pathogenic Polycystic kidney disease 4 2022-05-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003396367 SCV004120136 likely pathogenic PKHD1-related disorder 2023-05-01 criteria provided, single submitter clinical testing The PKHD1 c.3467C>T variant is predicted to result in the amino acid substitution p.Ser1156Leu. This variant has been reported in many individuals with autosomal recessive polycystic kidney disease (Bergmann et al 2005. PubMed ID: 15698423; Gunay-Aygun M et al 2009. PubMed ID: 19914852; Melchionda S et al 2016. PubMed ID: 27225849; Tong YQ et al 2016. PubMed ID: 27752906; Gately R et al 2020. PubMed ID: 33426401; Mallawaarachchi AC et al 2021. PubMed ID: 33437033; Burgmaier K et al 2021. PubMed ID: 33940108). This variant is reported in 0.0062% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51893047-G-A). This variant is interpreted as likely pathogenic.
Baylor Genetics RCV001810487 SCV004204549 likely pathogenic Polycystic kidney disease 4 2023-09-10 criteria provided, single submitter clinical testing
Natera, Inc. RCV001027935 SCV001190665 likely pathogenic Polycystic kidney disease 2019-05-20 no assertion criteria provided clinical testing
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center RCV001844845 SCV001876963 uncertain significance Autosomal dominant polycystic liver disease 2021-09-01 no assertion criteria provided research

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