ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10628T>C (p.Leu3543Ser) (rs1554183398)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557856 SCV000629900 uncertain significance Autosomal recessive polycystic kidney disease 2017-01-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 3543 of the PKHD1 protein (p.Leu3543Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with autosomal recessive polycystic kidney disease (PMID: 15698423). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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