ClinVar Miner

Submissions for variant NM_001139.3(ALOX12B):c.1579G>A (p.Val527Met)

gnomAD frequency: 0.00006  dbSNP: rs199545653
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000421593 SCV000521132 likely pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27025581, 17139268, 19890349, 26762237, 34426522, 31168818, 35315045, 33435499)
SIB Swiss Institute of Bioinformatics RCV000193750 SCV000803495 likely pathogenic Autosomal recessive congenital ichthyosis 2 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Ichthyosis, congenital, autosomal recessive 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => found in unrelated patients (PMID:26762237) (PMID:17139268) (PMID:19890349). PM3 => For recessive disorders, detected in trans with a likely pathogenic variant (PMID:26762237).
Invitae RCV000421593 SCV002142346 pathogenic not provided 2023-10-07 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 527 of the ALOX12B protein (p.Val527Met). This variant is present in population databases (rs199545653, gnomAD 0.02%). This missense change has been observed in individuals with congenital ichthyosis (PMID: 17139268, 27025581). ClinVar contains an entry for this variant (Variation ID: 212729). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ALOX12B protein function. For these reasons, this variant has been classified as Pathogenic.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000193750 SCV000223920 likely pathogenic Autosomal recessive congenital ichthyosis 2 2014-11-19 no assertion criteria provided clinical testing
Institute for Human Genetics, University Medical Center Freiburg RCV000193750 SCV001477962 pathogenic Autosomal recessive congenital ichthyosis 2 2021-01-07 no assertion criteria provided clinical testing

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