ClinVar

Description

The R108L variant has also been reproted previously in two individuals classical citrullinemia (Vilaseca et al., 2001; Häberle et al. 2002). One individual was compound heterozygous for a pathogenic in ASS1 and in the other individual; R108L was found in cis with a different variant in the ASS1 gene and another variant was not identified by sequencing the other allele (Häberle et al. 2002; Vilaseca et al., 2001). 1000 Genomes reports R108Lwas observed in 17/1322 alleles from individuals of African background, including 8/212 alleles from individuals of Luhya, Kenya, with one individual reported as homozygous, indicating it may be a rare, benign variant in these populations. The R108L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.