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]
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NC_012920.1:m.13379A>C

CA414817724

986501 (ClinVar)

Gene: MT-ND5
Condition: mitochondrial disease
Inheritance Mode: Mitochondrial inheritance
Link to MONDO
UUID: 6615f92f-9cef-49d4-907a-f251742f99d8
Approved on: 2022-06-30
Published on: 2022-06-30

HGVS expressions

NC_012920.1:m.13379A>C
J01415.2:m.13379A>C
ENST00000361567.2:c.1043A>C

Uncertain Significance

Met criteria codes 2
PP3 PM2_Supporting
Not Met criteria codes 8
PVS1 PS1 PS2 PS3 PS4 PM6 PM5 PP1

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Mitochondrial Diseases VCEP
The m.13379A>C (p.H348P) variant in MT-ND5 has been reported in one individual from one family (PMID: 17003408), in a male with LHON. The variant was present at homoplasmy in blood and haplogroup was M1. Although it is reported in this paper that this proband had a family history of poor vision, no details are provided. 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 0.80 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). There are no functional studies 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 Mitochondrial Disease Variant Curation Expert Panel on May 3, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PM2_supporting, PP3.
Met criteria codes
PP3
The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.80 (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
PVS1
This is a missense variant.
PS1
No other variants resulting in the same amino acid change are reported.
PS2
Family history information is not reported for the single case reported (Abu-Amero et al., 2006).
PS3
There are no functional studies reported for this variant.
PS4
The m.13379A>C (p.H348P) variant in MT-ND5 has been reported in one individual from one family (PMID: 17003408), in a male with LHON. The variant was present at homoplasmy in blood and haplogroup was M1.
PM6
Family history information is not reported for the single case reported (Abu-Amero et al., 2006).
PM5
m.13379A>G (p.H348R) has been reported to be associated with LHON, however evidence did not meet criteria to be classified as pathogenic or likely pathogenic.
PP1
Family history information is not reported for the single case reported (Abu-Amero et al., 2006).
Curation History
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