ClinVar Miner

Submissions for variant NM_001139.3(ALOX12B):c.1790C>A (p.Ala597Glu)

gnomAD frequency: 0.00005  dbSNP: rs752509098
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255637 SCV000321402 likely pathogenic not provided 2023-08-15 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29444371, 27025581, 31168818, 19890349, 33435499, 31046801, 29687370)
CeGaT Center for Human Genetics Tuebingen RCV000255637 SCV001248906 pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV000255637 SCV003260745 pathogenic not provided 2023-04-29 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALOX12B protein function. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 265039). This missense change has been observed in individual(s) with autosomal recessive congenital ichthyosis (PMID: 19890349, 31168818, 33435499; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs752509098, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 597 of the ALOX12B protein (p.Ala597Glu).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155138 SCV003844620 pathogenic Lamellar ichthyosis 2024-03-14 criteria provided, single submitter clinical testing Variant summary: ALOX12B c.1790C>A (p.Ala597Glu) results in a non-conservative amino acid change located in the Lipoxygenase, C-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251456 control chromosomes (gnomAD). c.1790C>A has been reported in the literature in multiple individuals affected with Lamellar Ichthyosis (e.g. Valquist_2010, Volozonoka_2018, Simpson_2020, Hotz_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33435499, 31168818, 19890349, 29687370). ClinVar contains an entry for this variant (Variation ID: 265039). Based on the evidence outlined above, the variant was classified as pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV001289939 SCV004015131 likely pathogenic Autosomal recessive congenital ichthyosis 2 criteria provided, single submitter clinical testing
Institute for Human Genetics, University Medical Center Freiburg RCV001289939 SCV001477943 pathogenic Autosomal recessive congenital ichthyosis 2 2021-01-07 no assertion criteria provided clinical testing

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