ClinVar Miner

Submissions for variant NM_012123.4(MTO1):c.402_403del (p.Tyr134_Lys135delinsTer)

dbSNP: rs769532203
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001797393 SCV002038897 pathogenic not provided 2021-12-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29331171)
PreventionGenetics, part of Exact Sciences RCV003401722 SCV004110926 likely pathogenic MTO1-related disorder 2023-05-05 criteria provided, single submitter clinical testing The MTO1 c.402_403delTA variant is predicted to result in premature protein termination (p.Tyr134*). This variant was reported in a compound heterozygous individual with MTO1 deficiency (Patient 9, O'Byrne et al 2018. PubMed ID: 29331171). This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-74176113-CTA-C). Truncating variants in MTO1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003533032 SCV004293772 pathogenic Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency 2022-11-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1328761). This premature translational stop signal has been observed in individual(s) with combined oxidative phosphorylation deficiency (PMID: 29331171). This variant is present in population databases (rs769532203, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr134*) in the MTO1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTO1 are known to be pathogenic (PMID: 22608499, 25058219).

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