ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.9820A>G (p.Lys3274Glu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003071862 SCV003457285 uncertain significance Autosomal recessive polycystic kidney disease 2022-02-06 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 3274 of the PKHD1 protein (p.Lys3274Glu). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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.
Ambry Genetics RCV003067542 SCV003668891 uncertain significance Inborn genetic diseases 2022-12-15 criteria provided, single submitter clinical testing The c.9820A>G (p.K3274E) alteration is located in exon 58 (coding exon 57) of the PKHD1 gene. This alteration results from a A to G substitution at nucleotide position 9820, causing the lysine (K) at amino acid position 3274 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003898750 SCV004714143 uncertain significance PKHD1-related disorder 2024-02-19 criteria provided, single submitter clinical testing The PKHD1 c.9820A>G variant is predicted to result in the amino acid substitution p.Lys3274Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% 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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