ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.2966T>C (p.Ile989Thr) (rs61750427)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695854 SCV000824376 uncertain significance Peroxisome biogenesis disorder 1A (Zellweger) 2018-05-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 989 of the PEX1 protein (p.Ile989Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs61750427, ExAC 0.07%). This variant has been reported in combination with a PEX1 pathogenic variant in several individuals affected with Zellweger syndrome (PMID: 27302843, 16088892). ClinVar contains an entry for this variant (Variation ID: 224325). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Leeds Amelogenesis Imperfecta Research Group, University of Leeds RCV000240787 SCV000264808 pathogenic Deafness enamel hypoplasia nail defects 2015-10-01 criteria provided, single submitter research Paper reports individual compound heterozygous for this variant

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