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NM_000116.5(TAFAZZIN):c.310T>C (p.Phe104Leu) AND 3-Methylglutaconic aciduria type 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 15, 2012
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:
RCV000035090.5

Allele description [Variation Report for NM_000116.5(TAFAZZIN):c.310T>C (p.Phe104Leu)]

NM_000116.5(TAFAZZIN):c.310T>C (p.Phe104Leu)

Gene:
TAFAZZIN:tafazzin, phospholipid-lysophospholipid transacylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000116.5(TAFAZZIN):c.310T>C (p.Phe104Leu)
HGVS:
  • NC_000023.11:g.154413507T>C
  • NG_009634.1:g.6968T>C
  • NG_009634.2:g.6973T>C
  • NG_012884.2:g.3582A>G
  • NM_000116.5:c.310T>CMANE SELECT
  • NM_001303465.2:c.364T>C
  • NM_181311.4:c.310T>C
  • NM_181312.4:c.310T>C
  • NM_181313.4:c.310T>C
  • NP_000107.1:p.Phe104Leu
  • NP_001290394.1:p.Phe122Leu
  • NP_851828.1:p.Phe104Leu
  • NP_851829.1:p.Phe104Leu
  • NP_851830.1:p.Phe104Leu
  • LRG_131t1:c.310T>C
  • LRG_131:g.6973T>C
  • LRG_131p1:p.Phe104Leu
  • NC_000023.10:g.153641844T>C
  • NM_000116.3:c.310T>C
  • NR_024048.3:n.721T>C
  • c.310T>C
Protein change:
F104L
Links:
dbSNP: rs397515741
NCBI 1000 Genomes Browser:
rs397515741
Molecular consequence:
  • NM_000116.5:c.310T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001303465.2:c.364T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181311.4:c.310T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181312.4:c.310T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181313.4:c.310T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_024048.3:n.721T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
3-Methylglutaconic aciduria type 2 (BTHS)
Synonyms:
Barth syndrome; 3-methylglutaconicaciduria type II; MGA type II; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010543; MedGen: C0574083; Orphanet: 111; OMIM: 302060

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000058730Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Mar 15, 2012) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Barth syndrome mutations that cause tafazzin complex lability.

Claypool SM, Whited K, Srijumnong S, Han X, Koehler CM.

J Cell Biol. 2011 Feb 7;192(3):447-62. doi: 10.1083/jcb.201008177.

PubMed [citation]
PMID:
21300850
PMCID:
PMC3101092

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000058730.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The Phe104Leu variant (TAZ) has not been previously reported, but appears to hav e occurred de novo in 1 individual with clinical features of Barth syndrome test ed by our laboratory. Phenylalanine (Phe) is highly conserved across evolutionar ily distant species, increasing the likelihood that a change would not be tolera ted. Computational tools (PolyPhen2, SIFT) predict that a change to Leu would im pact the protein, though the accuracy of these tools is unknown. Another variant at the same position (Phe104Val) has been reported as occurring de novo in 1 in dividual with elevated MLCL levels (Tafazzin (TAZ) Gene Mutation Database) and y east constructs of this variant resulted in a significant accumulation of MLCLs (Claypool 2011). Collectively, this information supports that the Phe104Leu vari ant is highly likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 24, 2022