ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10973T>C (p.Ile3658Thr) (rs142536551)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733283 SCV000861329 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing
Invitae RCV000460905 SCV000545852 uncertain significance Autosomal recessive polycystic kidney disease 2016-09-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3658 of the PKHD1 protein (p.Ile3658Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs142536551, ExAC 0.06%) but has not been reported in the literature in individuals with a PKHD1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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