ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.7430T>G (p.Phe2477Cys)

gnomAD frequency: 0.00003  dbSNP: rs1366295189
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633422 SCV000754644 likely pathogenic Autosomal recessive polycystic kidney disease 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2477 of the PKHD1 protein (p.Phe2477Cys). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 33940108). 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: 528290). 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%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Eurofins Ntd Llc (ga) RCV000731567 SCV000859405 uncertain significance not provided 2018-01-26 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477389 SCV002801311 uncertain significance Polycystic kidney disease 4 2022-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000731567 SCV003852839 uncertain significance not provided 2022-09-28 criteria provided, single submitter clinical testing 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)
Natera, Inc. RCV000633422 SCV002078025 uncertain significance Autosomal recessive polycystic kidney disease 2018-09-14 no assertion criteria provided clinical testing

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