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NM_021830.5(TWNK):c.592C>G (p.Leu198Val) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jun 18, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV002654291.4

Allele description [Variation Report for NM_021830.5(TWNK):c.592C>G (p.Leu198Val)]

NM_021830.5(TWNK):c.592C>G (p.Leu198Val)

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.592C>G (p.Leu198Val)
HGVS:
  • NC_000010.11:g.100988802C>G
  • NG_011646.1:g.3714G>C
  • NG_012624.1:g.6267C>G
  • NM_001163812.2:c.592C>G
  • NM_001163813.2:c.-119-842C>G
  • NM_001163814.2:c.-119-842C>G
  • NM_001368275.1:c.-57-904C>G
  • NM_021830.4:c.592C>G
  • NM_021830.5:c.592C>GMANE SELECT
  • NP_001157284.1:p.Leu198Val
  • NP_068602.2:p.Leu198Val
  • NP_068602.2:p.Leu198Val
  • NC_000010.10:g.102748559C>G
  • NM_021830.3:c.592C>G
  • NR_160738.1:n.1260C>G
  • NR_160740.1:n.1260C>G
  • NR_160741.1:n.1260C>G
  • NR_160742.1:n.1260C>G
Protein change:
L198V
Molecular consequence:
  • NM_001163813.2:c.-119-842C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001163814.2:c.-119-842C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001368275.1:c.-57-904C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001163812.2:c.592C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021830.5:c.592C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_160738.1:n.1260C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160740.1:n.1260C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160741.1:n.1260C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160742.1:n.1260C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002987716Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 10, 2023) 		germlineclinical testing

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

SCV005081422GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Jun 18, 2024) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV002987716.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 198 of the TWNK protein (p.Leu198Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TWNK-related conditions. ClinVar contains an entry for this variant (Variation ID: 1947200). 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TWNK protein function.

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

From GeneDx, SCV005081422.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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

Last Updated: Sep 29, 2024