ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.4105C>T (p.Arg1369Cys)

gnomAD frequency: 0.00004  dbSNP: rs368974211
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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) RCV000314188 SCV000342750 uncertain significance not provided 2016-06-21 criteria provided, single submitter clinical testing
Invitae RCV000705749 SCV000834762 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1369 of the PKHD1 protein (p.Arg1369Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs368974211, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 288588). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV002487257 SCV002794246 uncertain significance Polycystic kidney disease 4 2022-01-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003910013 SCV004735299 uncertain significance PKHD1-related disorder 2023-11-22 criteria provided, single submitter clinical testing The PKHD1 c.4105C>T variant is predicted to result in the amino acid substitution p.Arg1369Cys. This variant has been reported along with a second PKHD1 variant in a patient with Caroli syndrome (Mavlikeev et al. 2019. PubMed ID: 30343465). This variant is reported in 0.020% 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.
Natera, Inc. RCV000705749 SCV002080965 uncertain significance Autosomal recessive polycystic kidney disease 2018-10-30 no assertion criteria provided clinical testing

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