U.S. flag

An official website of the United States government

NM_004614.5(TK2):c.323C>T (p.Thr108Met) AND Mitochondrial DNA depletion syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 23, 2024
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:
RCV003993743.1

Allele description [Variation Report for NM_004614.5(TK2):c.323C>T (p.Thr108Met)]

NM_004614.5(TK2):c.323C>T (p.Thr108Met)

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.323C>T (p.Thr108Met)
Other names:
p.T108M:ACG>ATG
HGVS:
  • NC_000016.10:g.66531432G>A
  • NG_016862.1:g.23981C>T
  • NM_001172643.1:c.230C>T
  • NM_001172644.2:c.248C>T
  • NM_001172645.2:c.269C>T
  • NM_001271934.2:c.176C>T
  • NM_001271935.1:c.230C>T
  • NM_001272050.2:c.32C>T
  • NM_004614.5:c.323C>TMANE SELECT
  • NP_001166114.1:p.Thr77Met
  • NP_001166115.1:p.Thr83Met
  • NP_001166116.1:p.Thr90Met
  • NP_001258863.1:p.Thr59Met
  • NP_001258864.1:p.Thr77Met
  • NP_001258979.1:p.Thr11Met
  • NP_004605.4:p.Thr108Met
  • NC_000016.9:g.66565335G>A
  • NM_001271934.2:c.176C>T
  • NM_004614.4:c.323C>T
  • NR_073520.2:n.1312C>T
  • O00142:p.Thr108Met
Protein change:
T108M; THR108MET
Links:
UniProtKB: O00142#VAR_019420; OMIM: 188250.0003; dbSNP: rs137854431
NCBI 1000 Genomes Browser:
rs137854431
Molecular consequence:
  • NM_001172643.1:c.230C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001172644.2:c.248C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001172645.2:c.269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271934.2:c.176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271935.1:c.230C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001272050.2:c.32C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004614.5:c.323C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_073520.2:n.1312C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Mitochondrial DNA depletion syndrome
Synonyms:
mitochondrial DNA depletion
Identifiers:
MONDO: MONDO:0018158; MedGen: C0342782; OMIM: PS603041

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004814035Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Feb 23, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy.

Cámara Y, Carreño-Gago L, Martín MA, Melià MJ, Blázquez A, Delmiro A, Garrabou G, Morén C, Díaz-Manera J, Gallardo E, Bornstein B, López-Gallardo E, Hernández-Lain A, San Millán B, Cancho E, Rodríguez-Vico JS, Martí R, García-Arumí E.

Neurology. 2015 Jun 2;84(22):2286-8. doi: 10.1212/WNL.0000000000001644. Epub 2015 May 6. No abstract available.

PubMed [citation]
PMID:
25948719

Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes.

Wang L, Limongelli A, Vila MR, Carrara F, Zeviani M, Eriksson S.

Mol Genet Metab. 2005 Jan;84(1):75-82.

PubMed [citation]
PMID:
15639197

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004814035.1

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

Description

Variant summary: TK2 c.323C>T (p.Thr108Met) results in a non-conservative amino acid change located in the deoxynucleoside kinase domain (IPR031314) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251080 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TK2 causing TK2-Related Mitochondrial DNA Depletion Syndrome (4.4e-05 vs 0.0011), allowing no conclusion about variant significance. c.323C>T has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with TK2-Related Mitochondrial DNA Depletion Syndrome (e.g. Wang_2005, Camara_2015). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Wang_2005). The most pronounced variant effect results in <10% of enzyme activity versus the WT protein. The following publications have been ascertained in the context of this evaluation (PMID: 25948719, 15639197). ClinVar contains an entry for this variant (Variation ID: 12710). Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024