NM_001144869.3(LIPT2):c.314T>G (p.Leu105Arg) AND Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 16, 2018
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:: RCV000505511.7

Allele description [Variation Report for NM_001144869.3(LIPT2):c.314T>G (p.Leu105Arg)]

NM_001144869.3(LIPT2):c.314T>G (p.Leu105Arg)

Genes:

LIPT2-AS1:LIPT2 antisense RNA 1 [Gene - HGNC]
LIPT2:lipoyl(octanoyl) transferase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001144869.3(LIPT2):c.314T>G (p.Leu105Arg)

Other names:

NM_001144869.1:c.314T>G(p.Leu105Arg)

HGVS:

NC_000011.10:g.74493390A>C
NG_051333.1:g.5324T>G
NM_001144869.3:c.314T>GMANE SELECT
NM_001329941.2:c.314T>G
NM_001329942.2:c.237+77T>G
NP_001138341.1:p.Leu105Arg
NP_001316870.1:p.Leu105Arg
LRG_1089t1:c.314T>G
LRG_1089:g.5324T>G
LRG_1089p1:p.Leu105Arg
NC_000011.9:g.74204435A>C
NM_001144869.2:c.314T>G

Protein change:

L105R; LEU105ARG

Links:

OMIM: 617659.0003; dbSNP: rs1190703859

NCBI 1000 Genomes Browser:

rs1190703859

Molecular consequence:

NM_001329942.2:c.237+77T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001144869.3:c.314T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001329941.2:c.314T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities
Synonyms:: LIPOYLTRANSFERASE 2 DEFICIENCY
Identifiers:: MONDO: MONDO:0060562; MedGen: C4540052; OMIM: 617668

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000599793	OMIM	no assertion criteria provided	Pathogenic (Sep 15, 2017)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000787454	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 16, 2018)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 28757203, 25741868
SCV001149825	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Jan 4, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000599793

OMIM

no assertion criteria provided

Pathogenic
(Sep 15, 2017)

germline

literature only

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

SCV000787454

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 16, 2018)

germline

curation

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

SCV001149825

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

criteria provided, single submitter

(Classification criteria August 2017)

Pathogenic
(Jan 4, 2018)

germline

clinical testing

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

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	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

Habarou F, Hamel Y, Haack TB, Feichtinger RG, Lebigot E, Marquardt I, Busiah K, Laroche C, Madrange M, Grisel C, Pontoizeau C, Eisermann M, Boutron A, Chrétien D, Chadefaux-Vekemans B, Barouki R, Bole-Feysot C, Nitschke P, Goudin N, Boddaert N, Nemazanyy I, Delahodde A, et al.

Am J Hum Genet. 2017 Aug 3;101(2):283-290. doi: 10.1016/j.ajhg.2017.07.001. Epub 2017 Jul 27.

PubMed [citation]

PMID:: 28757203
PMCID:: PMC5544388

Details of each submission

From OMIM, SCV000599793.1

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

Description

For discussion of the c.314T-G transversion (c.314T-G, NM_001144869.2) in exon 1 of the LIPT2 gene, resulting in a leu105-to-arg (L105R) substitution, that was found in compound heterozygous state in 2 sibs with neonatal severe encephalopathy with lactic acidosis and brain abnormalities (NELABA; 617668) by Habarou et al. (2017), see 617659.0001.

#	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 SIB Swiss Institute of Bioinformatics, SCV000787454.1

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

Description

This variant is interpreted as a Likely Pathogenic, for Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PS3 => Well-established functional studies show a deleterious effect (PMID:28757203). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:28757203).

#	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 Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001149825.1

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

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

Last Updated: Apr 20, 2024

ClinVar

Relating variation to medicine