NM_021830.5(TWNK):c.712A>G (p.Ile238Val) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 17, 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:: RCV001908856.6

Allele description [Variation Report for NM_021830.5(TWNK):c.712A>G (p.Ile238Val)]

NM_021830.5(TWNK):c.712A>G (p.Ile238Val)

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.712A>G (p.Ile238Val)

HGVS:

NC_000010.11:g.100988922A>G
NG_011646.1:g.3594T>C
NG_012624.1:g.6387A>G
NM_001163812.2:c.712A>G
NM_001163813.2:c.-119-722A>G
NM_001163814.2:c.-119-722A>G
NM_001368275.1:c.-57-784A>G
NM_021830.5:c.712A>GMANE SELECT
NP_001157284.1:p.Ile238Val
NP_068602.2:p.Ile238Val
NC_000010.10:g.102748679A>G
NR_160738.1:n.1380A>G
NR_160740.1:n.1380A>G
NR_160741.1:n.1380A>G
NR_160742.1:n.1380A>G

Protein change:

I238V

Links:

dbSNP: rs774241806

NCBI 1000 Genomes Browser:

rs774241806

Molecular consequence:

NM_001163813.2:c.-119-722A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001163814.2:c.-119-722A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001368275.1:c.-57-784A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001163812.2:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.712A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.1380A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.1380A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.1380A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.1380A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens diacylglycerol O-acyltransferase homolog 2 (mouse) (DGAT2), mRNA
Homo sapiens diacylglycerol O-acyltransferase homolog 2 (mouse) (DGAT2), mRNA
gi|14211870|ref|NM_032564.1|

Nucleotide
Concise Conserved Domain Links for Protein (Select 752685849) (1)
Conserved Domains
PIGG phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group) [...
PIGG phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group) [Homo sapiens]
Gene ID:54872

Gene
Gene Links for GEO Profiles (Select 74257747) (1)
Gene
OR8K5 olfactory receptor family 8 subfamily K member 5 [Homo sapiens]
OR8K5 olfactory receptor family 8 subfamily K member 5 [Homo sapiens]
Gene ID:219453

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002174218	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002174218

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 17, 2023)

germline

clinical testing

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

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

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, SCV002174218.4

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 238 of the TWNK protein (p.Ile238Val). This variant is present in population databases (rs774241806, gnomAD 0.004%). 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: 1403058). 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 not expected to disrupt TWNK protein function with a negative predictive value of 95%. 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: Sep 29, 2024

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