biostudies-literatureUnknown15Xiao D<h4>Objective</h4>To accurately verify the pathogenicity of variants of uncertain significance (VUS) in <i>MUT</i> and <i>MMACHC</i> genes through mass spectrometry and <i>silico</i> analysis.<h4>Methods</h4>This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of <i>MMUT</i> and <i>MMACHC</i> variants were analyzed using <i>silico</i> analysis.<h4>Results</h4>The percentage of those carrying VUS cases was 68.15% (659/967). In the <i>MFrontiers in genetics1403913https://www.ebi.ac.uk/biostudies/studies/S-EPMC11284102biostudies-literatureUsing metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.PMC11284102Li HSu CMiu TGu XXiao XZhou WLu FYe YYuan GLi ZLi SShi CZhang YHuang WWei TMa HDiao SZhuang GHao HXiao DWang YfalseUsing metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.<h4>Objective</h4>To accurately verify the pathogenicity of variants of uncertain significance (VUS) in <i>MUT</i> and <i>MMACHC</i> genes through mass spectrometry and <i>silico</i> analysis.<h4>Methods</h4>This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of <i>MMUT</i> and <i>MMACHC</i> variants were analyzed using <i>silico</i> analysis.<h4>Results</h4>The percentage of those carrying VUS cases was 68.15% (659/967). In the <i>M2024-01-01T00:00:00Z20242026-04-21T03:24:04.747Z2026-04-21T03:14:22.546ZS-EPMC112841023907617010.3389/fgene.2024.1403913