NM_022445.4(TPK1):c.566G>A (p.Gly189Glu) AND Childhood encephalopathy due to thiamine pyrophosphokinase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 14, 2019
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:: RCV001036676.8

Allele description [Variation Report for NM_022445.4(TPK1):c.566G>A (p.Gly189Glu)]

NM_022445.4(TPK1):c.566G>A (p.Gly189Glu)

Gene:

TPK1:thiamin pyrophosphokinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q35

Genomic location:

Preferred name:

NM_022445.4(TPK1):c.566G>A (p.Gly189Glu)

HGVS:

NC_000007.14:g.144548538C>T
NG_032112.2:g.292516G>A
NM_001042482.2:c.419G>A
NM_001350879.1:c.566G>A
NM_001350880.1:c.419G>A
NM_001350881.1:c.566G>A
NM_001350882.1:c.551G>A
NM_001350883.1:c.551G>A
NM_001350884.2:c.551G>A
NM_001350885.1:c.248G>A
NM_001350886.1:c.248G>A
NM_001350887.1:c.248G>A
NM_001350889.1:c.248G>A
NM_001350893.1:c.248G>A
NM_001350894.1:c.248G>A
NM_001350895.1:c.215G>A
NM_022445.4:c.566G>AMANE SELECT
NP_001035947.1:p.Gly140Glu
NP_001337808.1:p.Gly189Glu
NP_001337809.1:p.Gly140Glu
NP_001337810.1:p.Gly189Glu
NP_001337811.1:p.Gly184Glu
NP_001337812.1:p.Gly184Glu
NP_001337813.1:p.Gly184Glu
NP_001337814.1:p.Gly83Glu
NP_001337815.1:p.Gly83Glu
NP_001337816.1:p.Gly83Glu
NP_001337818.1:p.Gly83Glu
NP_001337822.1:p.Gly83Glu
NP_001337823.1:p.Gly83Glu
NP_001337824.1:p.Gly72Glu
NP_071890.2:p.Gly189Glu
NC_000007.13:g.144245631C>T
NM_022445.3:c.566G>A
NR_146934.1:n.463G>A
NR_146935.1:n.602G>A
NR_146936.2:n.915G>A

Protein change:

G140E

Links:

dbSNP: rs2063720083

NCBI 1000 Genomes Browser:

rs2063720083

Molecular consequence:

NM_001042482.2:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350879.1:c.566G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350880.1:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350881.1:c.566G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350882.1:c.551G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350883.1:c.551G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350884.2:c.551G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350885.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350886.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350887.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350889.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350893.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350894.1:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350895.1:c.215G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022445.4:c.566G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146934.1:n.463G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146935.1:n.602G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146936.2:n.915G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
Synonyms:: ENCEPHALOPATHY, EPISODIC, DUE TO THIAMINE PYROPHOSPHOKINASE DEFICIENCY; Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type)
Identifiers:: MONDO: MONDO:0013761; MedGen: C3280866; Orphanet: 293955; OMIM: 614458

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200052	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 14, 2019)	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

SCV001200052

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 14, 2019)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001200052.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TPK1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 189 of the TPK1 protein (p.Gly189Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.

#	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: Sep 29, 2024

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