ClinVar Miner

Submissions for variant NM_001144869.3(LIPT2):c.377T>G (p.Leu126Arg)

gnomAD frequency: 0.00020  dbSNP: rs753904927
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
SIB Swiss Institute of Bioinformatics RCV000505518 SCV000787469 likely pathogenic Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities 2018-04-16 criteria provided, single submitter curation This variant is interpreted as a Likely Pathogenic, for Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PS3 => Well-established functional studies show a deleterious effect (PMID:28757203). PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS4-Moderate => PS4 downgraded in strength to Moderate (PMID:28757203). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:28757203).
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000505518 SCV001149824 pathogenic Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities 2018-01-04 criteria provided, single submitter clinical testing
Invitae RCV001857235 SCV002199902 uncertain significance not provided 2022-09-19 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 438639). This missense change has been observed in individuals with neonatal encephalopathy with lactic acidosis and brain anomalies (PMID: 28757203). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs753904927, gnomAD 0.04%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 126 of the LIPT2 protein (p.Leu126Arg).
PreventionGenetics, part of Exact Sciences RCV003403183 SCV004111724 likely pathogenic LIPT2-related condition 2023-03-02 criteria provided, single submitter clinical testing The LIPT2 c.377T>G variant is predicted to result in the amino acid substitution p.Leu126Arg. This variant was reported in a compound heterozygous individual with severe neonatal encephalopathy (Habarou et al 2017. PubMed ID: 28757203). Biochemical and functional studies support pathogenicity for the c.377T>C change (Lebigot E et al 2017. PubMed ID: 28803783). This variant is reported in 0.045% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-74204372-A-C). This variant is interpreted as likely pathogenic.
OMIM RCV000505518 SCV000599791 pathogenic Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities 2017-09-16 no assertion criteria provided literature only

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