ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2264C>T (p.Pro755Leu)

dbSNP: rs1057517158
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000598488 SCV000709051 pathogenic not provided 2018-07-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000408967 SCV000894385 likely pathogenic Autosomal recessive polycystic kidney disease 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000408967 SCV003439445 pathogenic Autosomal recessive polycystic kidney disease 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 755 of the PKHD1 protein (p.Pro755Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with polycystic kidney disease (PMID: 15698423, 24162162, 31730820). 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: 371292). 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.
Baylor Genetics RCV003463802 SCV004204689 likely pathogenic Polycystic kidney disease 4 2024-03-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003463802 SCV005673588 likely pathogenic Polycystic kidney disease 4 2024-04-02 criteria provided, single submitter clinical testing
Counsyl RCV000408967 SCV000486839 likely pathogenic Autosomal recessive polycystic kidney disease 2016-08-22 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004748747 SCV005361821 likely pathogenic PKHD1-related disorder 2024-03-15 no assertion criteria provided clinical testing The PKHD1 c.2264C>T variant is predicted to result in the amino acid substitution p.Pro755Leu. In the compound heterozygous state with different pathogenic PKHD1 variants, this variant has been reported in individuals with autosomal recessive polycystic kidney disease (ARPKD) (Bergmann et al. 2005. PubMed ID: 15698423; Liang et al. 2019. PubMed ID: 31730820; Obeidova et al. 2015. PubMed ID: 26695994). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. This variant is interpreted as likely pathogenic.

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