Submissions for variant NM_020117.11(LARS1):c.743G>T (p.Cys248Phe)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004800216	SCV005422099	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2024-10-25	criteria provided, single submitter	clinical testing	Variant summary: LARS1 c.743G>T (p.Cys248Phe) results in a non-conservative amino acid change located in the Aminoacyl-tRNA synthetase, class Ia domain (IPR002300) of 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.743G>T has been reported in the literature in at-least one individual affected with Liver Failure Acute Infantile, Type 1 (example: Tabolacci_2021). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (example: Tabolacci_2021). The following publication has been ascertained in the context of this evaluation (PMID: 33314043). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.