NM_004614.5(TK2):c.311G>A (p.Arg104His) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 4, 2022
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:: RCV001882601.2

Allele description

NM_004614.5(TK2):c.311G>A (p.Arg104His)

Gene:

TK2:thymidine kinase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q21

Genomic location:

Preferred name:

NM_004614.5(TK2):c.311G>A (p.Arg104His)

HGVS:

NC_000016.10:g.66531444C>T
NG_016862.1:g.23969G>A
NM_001172643.1:c.218G>A
NM_001172644.2:c.236G>A
NM_001172645.2:c.257G>A
NM_001271934.2:c.164G>A
NM_001271935.1:c.218G>A
NM_001272050.2:c.20G>A
NM_004614.5:c.311G>AMANE SELECT
NP_001166114.1:p.Arg73His
NP_001166115.1:p.Arg79His
NP_001166116.1:p.Arg86His
NP_001258863.1:p.Arg55His
NP_001258864.1:p.Arg73His
NP_001258979.1:p.Arg7His
NP_004605.4:p.Arg104His
NC_000016.9:g.66565347C>T
NR_073520.2:n.1300G>A

Protein change:

R104H

Links:

dbSNP: rs770318536

NCBI 1000 Genomes Browser:

rs770318536

Molecular consequence:

NM_001172643.1:c.218G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001172644.2:c.236G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001172645.2:c.257G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271934.2:c.164G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271935.1:c.218G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001272050.2:c.20G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004614.5:c.311G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_073520.2:n.1300G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002188776	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29602790, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002188776

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 4, 2022)

germline

clinical testing

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

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

Retrospective natural history of thymidine kinase 2 deficiency.

Garone C, Taylor RW, Nascimento A, Poulton J, Fratter C, Domínguez-González C, Evans JC, Loos M, Isohanni P, Suomalainen A, Ram D, Hughes MI, McFarland R, Barca E, Lopez Gomez C, Jayawant S, Thomas ND, Manzur AY, Kleinsteuber K, Martin MA, Kerr T, Gorman GS, et al.

J Med Genet. 2018 Aug;55(8):515-521. doi: 10.1136/jmedgenet-2017-105012. Epub 2018 Mar 30.

PubMed [citation]

PMID:: 29602790
PMCID:: PMC6073909

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, SCV002188776.2

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 104 of the TK2 protein (p.Arg104His). This variant is present in population databases (rs770318536, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of TK2-related conditions (PMID: 29602790). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg104 amino acid residue in TK2. Other variant(s) that disrupt this residue have been observed in individuals with TK2-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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.

#	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 24, 2023

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