Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV000167581 | SCV002572770 | likely pathogenic | Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Start-lost is reinitiation of translation may occur at a downstream alternate start codon but still result in a loss or disruption of normal protein function as there have been pathogenic variants reported upstream of the alterante start codon. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 25393721). The variant has been reported to be associated with ECHS1-related disorder (ClinVar ID: VCV000156433 / PMID: 25393721). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Invitae | RCV002515942 | SCV003282326 | pathogenic | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the ECHS1 protein in which other variant(s) (p.Ala2Val) have been determined to be pathogenic (PMID: 25393721, 32677908, 33139125, 33163364). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that disruption of the initiator codon alters ECHS1 gene expression (PMID: 25393721). ClinVar contains an entry for this variant (Variation ID: 156433). Disruption of the initiator codon has been observed in individual(s) with Leigh syndrome (PMID: 25393721). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the ECHS1 mRNA. The next in-frame methionine is located at codon 103. |
| Department of Mental Retardation and Birth Defect Research, |
RCV000144496 | SCV000189814 | probable-pathogenic | Leigh syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. | |
| OMIM | RCV000167581 | SCV000218462 | pathogenic | Mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency | 2015-02-01 | no assertion criteria provided | literature only |