Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Unidad de Genómica Garrahan, |
RCV003484260 | SCV004231895 | likely pathogenic | MELAS syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | The m.15215G>A variant was found in a 14-year-old boy with stroke-like episodes, intellectual disability and hyperlactic acidemia (HP:0002401, HP:0001249, HP:0003128). The variant NC_012920.1:m.15215G>A (YP_003024038.1:p.Gly157*) in the MT-CYB gene is interpreted as Likely pathogenic according to the applied mitochondrial DNA-specific ACMG/AMP guidelines (PMID: 32906214). This variant meets the following evidence criteria: PVS1 strong: a stop variant, 15215G>A, predicting a gly157* truncation of the protein with loss of 223 amino acids, representing 59% of the C terminus of cytochrome b. PM2 supp: not found in population database (gnomAD, MITOmap) PS2 supp: the variant is de novo, since it was not detected in a blood sample from the mother studied by NGS (identical mitochondrial dna sequence). PM8: Heteroplasmy level among different patient tissues correlates with the clinical phenotype. Muscle Biopsy = 92%, Urinary Epithelial Cells = 87% and Blood = 51%. |