ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.4091A>G (p.Tyr1364Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003104893 SCV003783629 uncertain significance Autosomal recessive polycystic kidney disease 2022-05-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1364 of the PKHD1 protein (p.Tyr1364Cys). This variant is present in population databases (rs749952769, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003900937 SCV004714587 uncertain significance PKHD1-related disorder 2024-01-13 criteria provided, single submitter clinical testing The PKHD1 c.4091A>G variant is predicted to result in the amino acid substitution p.Tyr1364Cys. This variant has been reported in heterozygous state in absence of a second variant in patient with polycystic kidney disease (Table S3, Burgmaier et al. 2021. PubMed ID: 33940108). This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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