ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2005C>T (p.Arg669Cys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003097653 SCV003488932 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 669 of the PKHD1 protein (p.Arg669Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs375547868, ExAC 0.009%). 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 not 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 RCV003906511 SCV004721805 uncertain significance PKHD1-related disorder 2024-02-28 criteria provided, single submitter clinical testing The PKHD1 c.2005C>T variant is predicted to result in the amino acid substitution p.Arg669Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% 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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