Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute Of Human Genetics Munich, |
RCV000578401 | SCV000680296 | likely pathogenic | Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency | 2017-11-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000578401 | SCV001539061 | uncertain significance | Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency | 2022-05-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 313 of the MTO1 protein (p.Arg313Gln). This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon. This variant is present in population databases (rs371179032, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of autosomal recessive combined oxidative phosphorylation deficiency (PMID: 30369941). ClinVar contains an entry for this variant (Variation ID: 488550). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |