NC_012920.1(MT-ND1):m.4160T>C AND Leber optic atrophy

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 4, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000010372.5

Allele description [Variation Report for NC_012920.1(MT-ND1):m.4160T>C]

NC_012920.1(MT-ND1):m.4160T>C

Gene:

MT-ND1:mitochondrially encoded NADH dehydrogenase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

NC_012920.1(MT-ND1):m.4160T>C

HGVS:

NC_012920.1:m.4160T>C
YP_003024026.1:p.Leu285Pro
AC_000021.2:m.4160T>C
NC_012920.1:g.4160T>C

Links:

OMIM: 516000.0002; dbSNP: rs199476119

NCBI 1000 Genomes Browser:

rs199476119

Condition(s)

Name:: Leber optic atrophy (LHON)
Synonyms:: Optic Atrophy, Hereditary, Leber; Leber hereditary optic neuropathy; Leber's disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010788; MedGen: C0917796; Orphanet: 104; OMIM: 535000; Human Phenotype Ontology: HP:0001112

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030598	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 1991)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000086637	GeneReviews	no classification provided	not provided	maternal	literature only	PubMed (2) [See all records that cite these PMIDs] 30143805, 20301353
SCV002517668	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Pathogenic (May 4, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030598

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 1991)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000086637

GeneReviews

no classification provided

not provided

maternal

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV002517668

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Pathogenic
(May 4, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees.

Howell N, Bindoff LA, McCullough DA, Kubacka I, Poulton J, Mackey D, Taylor L, Turnbull DM.

Am J Hum Genet. 1991 Nov;49(5):939-50.

PubMed [citation]

PMID:: 1928099
PMCID:: PMC1683233

Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches.

Jurkute N, Majander A, Bowman R, Votruba M, Abbs S, Acheson J, Lenaers G, Amati-Bonneau P, Moosajee M, Arno G, Yu-Wai-Man P.

Eur J Hum Genet. 2019 Mar;27(3):494-502. doi: 10.1038/s41431-018-0235-y. Epub 2018 Aug 24. No abstract available.

PubMed [citation]

PMID:: 30143805
PMCID:: PMC6460557

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000030598.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

This allele converts the highly conserved leucine 285 to a proline (L285P). This mutation has been found in 1 large Australian pedigree manifesting LHON (535000) and additional neurological symptoms, together with the primary MTND6*LHON14484C. The mutation was homoplasmic in that pedigree in which 76% of the maternal relatives were affected, 54% of which were males (Howell et al., 1991). See also variant 516000.0006.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000086637.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

This mitochondrial DNA variant affects function. It hase been identified in at least two independent LHON pedigrees and segregates with affected disease status.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV002517668.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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