Variant: m.12848C>T

CA340937

9704 (ClinVar)

Gene: N/A

Condition: mitochondrial disease

Inheritance Mode: Mitochondrial inheritance

UUID: a5214e2f-36a4-4643-ab2e-fc071378d55a

Approved on: 2023-11-28

Published on: 2025-06-05

HGVS expressions

NC_012920.1:m.12848C>T
J01415.2:m.12848C>T
ENST00000361567.2:c.512C>T

Uncertain Significance

• Met criteria codes: PM2_Supporting PP3

• Not Met criteria codes: PP1

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Criteria Specification: ClinGen Mitochondrial Disease Nuclear and Mitochondrial Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1_mtDNA

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The m.12848C>T (p.A171V) variant in MT-ND5 has been reported in one individual with primary mitochondrial disease to date, in a man with Leber Hereditary Optic Neuropathy (LHON). The variant was present at 54% heteroplasmy in blood (PMID: 16240359). The variant was present in his asymptomatic mother at 37% heteroplasmy in blood. This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). The computational predictor APOGEE suggests this variant is pathogenic (0.95, range 0-1; PP3). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on November 28, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PP3.

Met criteria codes

• PM2_Supporting: This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting).
• PP3: The computational predictor APOGEE suggests this variant is pathogenic (0.95, range 0-1; PP3).

Not Met criteria codes

• PP1: The variant was present in his asymptomatic mother at 37% heteroplasmy in blood.