ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5984A>G (p.Glu1995Gly) (rs1554144359)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000550974 SCV000629928 uncertain significance Autosomal recessive polycystic kidney disease 2018-03-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 1995 of the PKHD1 protein (p.Glu1995Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant occurs with a pathogenic variant (p.Trp3871*) in an individual with polycystic kidney disease (Invitae). Family studies indicate these two variants are on opposite chromosomes, which suggests the c.5984A>G substitution may contribute to disease. This variant also occurs with p.Trp3871* in another affected individual (PMID: 11919560) in whom it is unknown whether the variants are on the same or opposite chromosomes. 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 affected individuals, 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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