ClinVar Miner

Submissions for variant NM_012123.4(MTO1):c.1450C>T (p.Arg484Trp)

gnomAD frequency: 0.00004  dbSNP: rs748152539
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000463868 SCV000547859 pathogenic Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency 2022-10-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MTO1 protein function. ClinVar contains an entry for this variant (Variation ID: 408272). This missense change has been observed in individual(s) with combined oxidative phosphorylation deficiency 10 (PMID: 29331171, 30831263, 31451716, 31842146). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs748152539, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 484 of the MTO1 protein (p.Arg484Trp).
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000463868 SCV000680301 pathogenic Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency 2017-10-25 criteria provided, single submitter clinical testing
GeneDx RCV001584154 SCV001820467 likely pathogenic not provided 2023-07-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30831263, 29331171, 33258288, 31842146, Almeida2023_Article, 31451716)
Fulgent Genetics, Fulgent Genetics RCV000463868 SCV002807339 likely pathogenic Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency 2021-11-11 criteria provided, single submitter clinical testing

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