ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5410C>T (p.Arg1804Cys)

dbSNP: rs201906247
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000598361 SCV000707407 uncertain significance not provided 2018-06-05 criteria provided, single submitter clinical testing
Counsyl RCV000665545 SCV000789687 uncertain significance Autosomal recessive polycystic kidney disease 2017-02-09 criteria provided, single submitter clinical testing
GeneDx RCV000598361 SCV001985429 uncertain significance not provided 2021-04-05 criteria provided, single submitter clinical testing Identified in a patient with ARPKD with a second variant in an unknown phase in published literature (Sharp et al., 2005); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15805161)
Invitae RCV000665545 SCV003250282 uncertain significance Autosomal recessive polycystic kidney disease 2021-11-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1804 of the PKHD1 protein (p.Arg1804Cys). This variant is present in population databases (rs201906247, gnomAD 0.08%). This missense change has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 15805161). ClinVar contains an entry for this variant (Variation ID: 501154). 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 RCV003420040 SCV004115791 uncertain significance PKHD1-related condition 2022-12-24 criteria provided, single submitter clinical testing The PKHD1 c.5410C>T variant is predicted to result in the amino acid substitution p.Arg1804Cys. This variant has been reported with a canonical splice variant (c.5381-2A>C) in a fetal specimen due to suspected autosomal recessive polycystic kidney disease (ARPKD) (Sharp et al. 2005. PubMed ID: 15805161). This variant was also described in a large cohort of individuals with suspected early-onset chronic kidney disease (Domingo-Gallego et al. 2022. PubMed ID: 33532864, supplementary data). This variant is reported in 0.078% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51882398-G-A). This variant could be pathogenic. At this time, however, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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