Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • There was no gene found in the curated document received from the VCI/VCEP
  • Gene listed was thus derived from ClinVar and/or CAR
  • The variant label for this record ("m.12706T>C") does not appear to be in HGVS format

Variant: m.12706T>C

CA120628

9698 (ClinVar)

Gene: MT-ND5
Condition: mitochondrial disease
Inheritance Mode: Mitochondrial inheritance
Link to MONDO
UUID: 65f6d23f-1a7e-4870-b49e-ca0a9fb875d3
Approved on: 2022-06-30
Published on: 2022-06-30

HGVS expressions

NC_012920.1:m.12706T>C
J01415.2:m.12706T>C
ENST00000361567.2:n.370T>C

Likely Pathogenic

Met criteria codes 4
PS4_Moderate PS2_Moderate PP3 PM2_Supporting
Not Met criteria codes 1
PS3

Evidence Links 0

Expert Panel

Criteria Specification Information

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The m.12706T>C (p.F124L) variant in MT-ND5 has been reported in at least seven unrelated individuals with primary mitochondrial disease and features including Leigh syndrome, MELAS and MELAS-like, and ophthalmoplegia (PS4_moderate; PMIDs: 34200828, 17317336, 21364701, 23847141, 14684687, 11938446). There is one report of a de novo occurrence of this variant (PS2_moderate, PMID: 17317336). This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.9 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). There are no cybrid studies, single fiber studies, or other functional assays reported. In summary, this variant meets criteria to be classified as likely pathogenic for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 Mitochondrial Disease Variant Curation Expert Panel on April 11, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PS4_moderate, PS2_moderate, PM2_supporting, PP3.
Met criteria codes
PS4_Moderate
The m.12706T>C (p.F124L) variant in MT-ND5 has been reported in at least seven unrelated individuals with primary mitochondrial disease and features including Leigh syndrome, MELAS and MELAS-like, and ophthalmoplegia (PS4_moderate; PMIDs: 34200828, 17317336, 21364701, 23847141, 14684687, 11938446).
PS2_Moderate
There is one report of a de novo occurrence of this variant (PS2_moderate, PMID: 17317336).
PP3
The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.9 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3).
PM2_Supporting
This variant is absent in the GenBank dataset, Helix dataset, and gnomAD v3.1.2 (PM2_supporting).
Not Met criteria codes
PS3
There are no cybrid studies, single fiber studies, or other functional assays reported.
Curation History
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