m.3635G>A AND Leber optic atrophy

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 4, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000055707.5

Allele description [Variation Report for m.3635G>A]

m.3635G>A

Gene:

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

Variant type:

single nucleotide variant

Genomic location:

Preferred name:

m.3635G>A

HGVS:

NC_012920.1:m.3635G>A
AC_000021.2:m.3635G>A
NC_012920.1:g.3635G>A

Links:

dbSNP: rs397515507

NCBI 1000 Genomes Browser:

rs397515507

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
SCV000086633	GeneReviews	no classification provided	not provided	maternal	literature only	PubMed (2) [See all records that cite these PMIDs] 30143805, 20301353
SCV000996715	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	criteria provided, single submitter (Modified ACMG Guidelines (Unpublished))	Likely pathogenic (Oct 17, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11479733, 25194554, 15972314, 19497304 Citation Link,
SCV002517663	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

SCV000086633

GeneReviews

no classification provided

not provided

maternal

literature only

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

SCV000996715

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

criteria provided, single submitter

(Modified ACMG Guidelines (Unpublished))

Likely pathogenic
(Oct 17, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV002517663

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	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

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

Leber Hereditary Optic Neuropathy.

Yu-Wai-Man P, Chinnery PF.

2000 Oct 26 [updated 2021 Mar 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301353

See all PubMed Citations (6)

Details of each submission

From GeneReviews, SCV000086633.3

#	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 Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine, SCV000996715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The NC_012920.1:m.3635G>A (YP_003024026.1:p.Ser110Asn) variant in MTND1 gene is interpretated to be a Likely Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PS1, PM10, PP4

#	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

From Mendelics, SCV002517663.1

#	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: Dec 9, 2023

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