ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10384A>G (p.Ile3462Val)

gnomAD frequency: 0.00009  dbSNP: rs139742511
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588920 SCV000699841 uncertain significance not provided 2017-08-10 criteria provided, single submitter clinical testing Variant summary: The PKHD1 c.10384A>G (p.Ile3462Val) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to non-functioning tool). This variant was found in the large control database ExAC at a frequency of 0.0000413 (5/121142 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic PKHD1 variant (0.0070711). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV001829630 SCV002211368 uncertain significance Autosomal recessive polycystic kidney disease 2021-11-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3462 of the PKHD1 protein (p.Ile3462Val). This variant is present in population databases (rs139742511, gnomAD 0.02%). 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: 496513). 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.
Fulgent Genetics, Fulgent Genetics RCV002483571 SCV002776155 uncertain significance Polycystic kidney disease 4 2021-12-28 criteria provided, single submitter clinical testing
Natera, Inc. RCV001829630 SCV002075519 uncertain significance Autosomal recessive polycystic kidney disease 2017-08-15 no assertion criteria provided clinical testing

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