Interpretation of SLC3A1 and SLC7A9 variants in cystinuria patients: The significance of the PM3 criterion and protein stability.

ABSTRACT: Cystinuria is a genetic disorder caused by defects in the b^0,+ transporter system, which is composed of rBAT and b^0,+AT coded by SLC3A1 and SLC7A9, respectively. Variants in SLC3A1 and SLC7A9 follow autosomal recessive inheritance and autosomal dominant inheritance with reduced penetrance, respectively, which complicates the interpretation of cystinuria-related variants. Here, we report seven different SLC3A1 variants and six different SLC7A9 variants. Among these variants were two novel variants previously not reported: SLC3A1 c.223C > T and SLC7A9 c.404A > G. In silico analysis using REVEL correlated well with the functional loss upon SLC7A9 variants with scores of 0.8560-0.9200 and 0.4970-0.5239 for severe and mild decrease in transport activity, respectively. In a

SUBMITTER: Lee B 

PROVIDER: S-EPMC10345071 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature