NM_004614.5(TK2):c.659T>C (p.Leu220Pro) AND not provided

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

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 23, 2023
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:: RCV001879750.3

Allele description

NM_004614.5(TK2):c.659T>C (p.Leu220Pro)

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.659T>C (p.Leu220Pro)

HGVS:

NC_000016.10:g.66513771A>G
NG_016862.1:g.41642T>C
NM_001172643.1:c.566T>C
NM_001172644.2:c.584T>C
NM_001172645.2:c.605T>C
NM_001271934.2:c.512T>C
NM_001271935.1:c.397T>C
NM_001272050.2:c.368T>C
NM_004614.5:c.659T>CMANE SELECT
NP_001166114.1:p.Leu189Pro
NP_001166115.1:p.Leu195Pro
NP_001166116.1:p.Leu202Pro
NP_001258863.1:p.Leu171Pro
NP_001258864.1:p.Ser133Pro
NP_001258979.1:p.Leu123Pro
NP_004605.4:p.Leu220Pro
NC_000016.9:g.66547674A>G
NC_000016.9:g.66547674A>G
NM_001172644.2:c.584T>C
NR_073520.2:n.1648T>C

Protein change:

L123P

Links:

dbSNP: rs1168827071

NCBI 1000 Genomes Browser:

rs1168827071

Molecular consequence:

NM_001172643.1:c.566T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172644.2:c.584T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001172645.2:c.605T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001271934.2:c.512T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001271935.1:c.397T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001272050.2:c.368T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004614.5:c.659T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_073520.2:n.1648T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Functional consequence:

Unknown function

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
SCV002301622	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 23, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29783828, 33013660, 35289132, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002301622

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 23, 2023)

germline

clinical testing

PubMed (4)
[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

[Thymidine kinase 2 gene compound heterozygous mutation leads to mitochondrial DNA depletion syndrome-2:a case report].

Wu Y, Liu DH, Zhang XX.

Zhonghua Er Ke Za Zhi. 2018 May 2;56(5):381-382. doi: 10.3760/cma.j.issn.0578-1310.2018.05.016. Chinese. No abstract available.

PubMed [citation]

PMID:: 29783828

Clinical Profile and Outcome of Pediatric Mitochondrial Myopathy in China.

Hu C, Li X, Zhao L, Shi Y, Zhou S, Wang Y.

Front Neurol. 2020;11:1000. doi: 10.3389/fneur.2020.01000.

PubMed [citation]

PMID:: 33013660
PMCID:: PMC7506116

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002301622.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TK2 protein function. ClinVar contains an entry for this variant (Variation ID: 972913). This missense change has been observed in individuals with TK2-related conditions (PMID: 29783828, 33013660, 35289132). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 220 of the TK2 protein (p.Leu220Pro).

#	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: Jul 23, 2024

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