ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.4465G>C (p.Asp1489His)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002726997 SCV003002036 uncertain significance Autosomal recessive polycystic kidney disease 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 1489 of the PKHD1 protein (p.Asp1489His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs764210835, ExAC 0.005%). This variant has not been reported in the literature in individuals with PKHD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV002726998 SCV003690722 uncertain significance Inborn genetic diseases 2021-07-20 criteria provided, single submitter clinical testing The c.4465G>C (p.D1489H) alteration is located in exon 32 (coding exon 31) of the PKHD1 gene. This alteration results from a G to C substitution at nucleotide position 4465, causing the aspartic acid (D) at amino acid position 1489 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003418596 SCV004115824 uncertain significance PKHD1-related disorder 2023-08-17 criteria provided, single submitter clinical testing The PKHD1 c.4465G>C variant is predicted to result in the amino acid substitution p.Asp1489His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51890143-C-G). 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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