ClinVar Miner

Submissions for variant NM_001191061.2(SLC25A22):c.754C>T (p.Arg252Trp)

dbSNP: rs1388811021
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000689898 SCV000817568 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2021-10-20 criteria provided, single submitter clinical testing 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. 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. This missense change has been observed in individuals with early infantile epileptic encephalopathy (PMID: 28454995). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 252 of the SLC25A22 protein (p.Arg252Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757772 SCV000886125 uncertain significance not provided 2018-05-30 criteria provided, single submitter clinical testing The SLC25A22 c.754C>T; p.Arg252Trp variant is reported in an individual with infantile epileptic encephalopathy in the homozygous state (Alfares 2017). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 252 is conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Considering available information, there is insufficient to classify this variant with certainty. Pathogenic SLC25A22 variants are causative for autosomal recessive early infantile epileptic encephalopathy (MIM: 609304). References: Alfares A et al. A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield. Mol Genet Metab. 2017 Jun;121(2):91-95.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000985196 SCV001133219 likely pathogenic Early myoclonic encephalopathy 2019-09-26 no assertion criteria provided clinical testing

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