Submissions for variant NM_001139.3(ALOX12B):c.769C>G (p.His257Asp)

dbSNP: rs1233776328

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001724288	SCV002265211	uncertain significance	not provided	2021-07-29	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with aspartic acid at codon 257 of the ALOX12B protein (p.His257Asp). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant has not been reported in the literature in individuals affected with ALOX12B-related conditions. ClinVar contains an entry for this variant (Variation ID: 995768). 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. 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.
Institute for Human Genetics, University Medical Center Freiburg	RCV001289977	SCV001477990	pathogenic	Autosomal recessive congenital ichthyosis 2	2021-01-07	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001724288	SCV001952674	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001724288	SCV001965301	likely pathogenic	not provided		no assertion criteria provided	clinical testing