U.S. flag

An official website of the United States government

NM_021830.5(TWNK):c.1609T>C (p.Tyr537His) AND TWNK-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 3, 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:
RCV004533016.1

Allele description [Variation Report for NM_021830.5(TWNK):c.1609T>C (p.Tyr537His)]

NM_021830.5(TWNK):c.1609T>C (p.Tyr537His)

Gene:
TWNK:twinkle mtDNA helicase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q24.31
Genomic location:
Preferred name:
NM_021830.5(TWNK):c.1609T>C (p.Tyr537His)
HGVS:
  • NC_000010.11:g.100990885T>C
  • NG_011646.1:g.1631A>G
  • NG_012624.1:g.8350T>C
  • NM_001163812.2:c.1609T>C
  • NM_001163813.2:c.247T>C
  • NM_001163814.2:c.247T>C
  • NM_001368275.1:c.247T>C
  • NM_021830.5:c.1609T>CMANE SELECT
  • NP_001157284.1:p.Tyr537His
  • NP_001157285.1:p.Tyr83His
  • NP_001157286.1:p.Tyr83His
  • NP_001355204.1:p.Tyr83His
  • NP_068602.2:p.Tyr537His
  • NC_000010.10:g.102750642T>C
  • NM_021830.4:c.1609T>C
  • NR_160738.1:n.2397T>C
  • NR_160739.1:n.557T>C
  • NR_160740.1:n.2215T>C
  • NR_160741.1:n.2215T>C
  • NR_160742.1:n.2335T>C
Protein change:
Y537H
Links:
dbSNP: rs144001072
NCBI 1000 Genomes Browser:
rs144001072
Molecular consequence:
  • NM_001163812.2:c.1609T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001163813.2:c.247T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001163814.2:c.247T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368275.1:c.247T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021830.5:c.1609T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_160738.1:n.2397T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160739.1:n.557T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160740.1:n.2215T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160741.1:n.2215T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160742.1:n.2335T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
TWNK-related disorder
Synonyms:
TWNK-related condition
Identifiers:

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
SCV004113941PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Sep 3, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004113941.1

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

Description

The TWNK c.1609T>C variant is predicted to result in the amino acid substitution p.Tyr537His. This variant was reported in the heterozygous state in individuals with chronic external ophthalmoplegia or Parkinson's disease; however, pathogenicity was not established (Ronchi et al. 2011. PubMed ID: 21689831; Percetti et al. 2022. PubMed ID: 35792653). This variant is reported in 0.029% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-102750642-T-C), which may be too frequent to be a primary cause of autosomal dominant disease. Although we suspect TWNK c.1609T>C (p.Tyr537His) may be benign, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Oct 12, 2025