ClinVar

Description

Variant summary: SLC25A13 c.1801G>A (p.Glu601Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251090 control chromosomes. c.1801G>A has been reported in the literature in the singly heterozygous or presumed compound heterozygous state in multiple individuals affected with Citrullinemia Type II (example, Kobayashi_2003, Chen_2013, Saheki_2002, Yamaguchi_2002, Fu_2011). These data indicate that the variant may be associated with disease. Functional analysis found that a yeast strain lacking the corresponding gene could not grow when this variant was introduced during complementation analysis, suggesting a lethal metabolic defect in this model system; protein levels were not impacted when strains were grown with adequate supplementation (example, Wongkittichote_2013). In patient cells presumed compound heterozygous with p.Leu85Pro protein levels were undetectable (example, Fu_2011) however the mechanism of protein loss/instability was not explored. The following publications have been ascertained in the context of this evaluation (PMID: 23901231, 20927635, 14680984, 12111366, 23053473, 11793471). ClinVar contains an entry for this variant (Variation ID: 21512). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.