Total submissions: 4
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, |
RCV000463868 | SCV000680301 | pathogenic | Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency | 2017-10-25 | criteria provided, single submitter | clinical testing | |
Gene |
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, |
RCV000463868 | SCV002807339 | likely pathogenic | Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency | 2021-11-11 | criteria provided, single submitter | clinical testing |