Submissions for variant NM_020117.11(LARS1):c.661C>T (p.Gln221Ter)

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	RCV002302561	SCV002598927	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2022-09-22	criteria provided, single submitter	clinical testing	Variant summary: LARS c.661C>T (p.Gln221X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic within ClinVar (e.g. c.3313C>T [p.Arg1105Ter]). The variant was absent in 225680 control chromosomes (gnomAD). To our knowledge, no occurrence of c.661C>T in individuals affected with Liver Failure Acute Infantile, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.