ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.847T>C (p.Phe283Leu)

dbSNP: rs375145340
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000592287 SCV000702484 uncertain significance not provided 2017-10-19 criteria provided, single submitter clinical testing
Invitae RCV001860162 SCV002301129 likely pathogenic Autosomal recessive polycystic kidney disease 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 283 of the PKHD1 protein (p.Phe283Leu). This variant is present in population databases (rs375145340, gnomAD 0.03%). This missense change has been observed in individuals with PKHD1-related conditions (PMID: 29095814, 33123899). ClinVar contains an entry for this variant (Variation ID: 497776). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PKHD1 protein function. 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.
PreventionGenetics, part of Exact Sciences RCV003403388 SCV004120145 likely pathogenic PKHD1-related condition 2022-09-20 criteria provided, single submitter clinical testing The PKHD1 c.847T>C variant is predicted to result in the amino acid substitution p.Phe283Leu. This variant has been reported in the compound heterozygous state with different truncating PKHD1 variants in two Chinese patients with autosomal recessive polycystic kidney disease (ARPKD) (Hu et al. 2018. PubMed ID: 29095814; Qiu et al. 2020. PubMed ID: 33123899). This variant is reported in 0.038% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51930807-A-G). This variant is interpreted as likely pathogenic.
Baylor Genetics RCV003465335 SCV004204728 uncertain significance Polycystic kidney disease 4 2023-02-11 criteria provided, single submitter clinical testing

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