NM_000116.5(TAFAZZIN):c.227C>G (p.Pro76Arg) AND 3-Methylglutaconic aciduria type 2

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 10, 2016
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:: RCV000230434.1

Allele description [Variation Report for NM_000116.5(TAFAZZIN):c.227C>G (p.Pro76Arg)]

NM_000116.5(TAFAZZIN):c.227C>G (p.Pro76Arg)

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.227C>G (p.Pro76Arg)

HGVS:

NC_000023.11:g.154412203C>G
NG_009634.1:g.5664C>G
NG_009634.2:g.5669C>G
NG_012884.2:g.4886G>C
NM_000116.5:c.227C>GMANE SELECT
NM_001303465.2:c.281C>G
NM_181311.4:c.227C>G
NM_181312.4:c.227C>G
NM_181313.4:c.227C>G
NP_000107.1:p.Pro76Arg
NP_001290394.1:p.Pro94Arg
NP_851828.1:p.Pro76Arg
NP_851829.1:p.Pro76Arg
NP_851830.1:p.Pro76Arg
LRG_131t1:c.227C>G
LRG_131:g.5669C>G
LRG_131p1:p.Pro76Arg
NC_000023.10:g.153640540C>G
NM_000116.3:c.227C>G
NR_024048.3:n.532C>G

Protein change:

P76R

Links:

dbSNP: rs878853654

NCBI 1000 Genomes Browser:

rs878853654

Molecular consequence:

NM_000116.5:c.227C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001303465.2:c.281C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181311.4:c.227C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181312.4:c.227C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_181313.4:c.227C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_024048.3:n.532C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000283511	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 10, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283511

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 10, 2016)

germline

clinical testing

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

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000283511.2

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

Description

This sequence change replaces proline with arginine at codon 76 of the TAZ protein (p.Pro76Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TAZ-related disease. Family studies indicate this missense variant likely was not inherited from either parent (i.e. occurred de novo) in an individual with disease (Invitae database). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In conclusion, this variant is absent from population databases, is predicted to be deleterious, and was shown to have occurred de novo. For these reasons, this variant has a been classified as Likely Pathogenic.

#	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: Apr 23, 2022

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