NM_021830.5(TWNK):c.793C>T (p.Arg265Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 15, 2021
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:: RCV001869311.4

Allele description [Variation Report for NM_021830.5(TWNK):c.793C>T (p.Arg265Cys)]

NM_021830.5(TWNK):c.793C>T (p.Arg265Cys)

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.793C>T (p.Arg265Cys)

HGVS:

NC_000010.11:g.100989003C>T
NG_011646.1:g.3513G>A
NG_012624.1:g.6468C>T
NM_001163812.2:c.793C>T
NM_001163813.2:c.-119-641C>T
NM_001163814.2:c.-119-641C>T
NM_001368275.1:c.-57-703C>T
NM_021830.5:c.793C>TMANE SELECT
NP_001157284.1:p.Arg265Cys
NP_068602.2:p.Arg265Cys
NP_068602.2:p.Arg265Cys
NC_000010.10:g.102748760C>T
NC_000010.10:g.102748760C>T
NM_021830.3:c.793C>T
NM_021830.4:c.793C>T
NR_160738.1:n.1461C>T
NR_160740.1:n.1461C>T
NR_160741.1:n.1461C>T
NR_160742.1:n.1461C>T

Protein change:

R265C

Links:

dbSNP: rs764669712

NCBI 1000 Genomes Browser:

rs764669712

Molecular consequence:

NM_001163813.2:c.-119-641C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001163814.2:c.-119-641C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001368275.1:c.-57-703C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001163812.2:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.793C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.1461C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.1461C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.1461C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.1461C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV002185752	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 15, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31055809, 27650058, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002185752

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 15, 2021)

germline

clinical testing

PubMed (3)
[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

[Clinical and genetic analysis of a patient with Perrault syndrome and additional neurological features].

Duan X, Wang W, Dong M, Wang L, Shao Z, Wang Z, Yuan Y, Wang R, Peng D.

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Jun 10;36(6):577-580. doi: 10.3760/cma.j.issn.1003-9406.2019.06.011. Chinese.

PubMed [citation]

PMID:: 31055809

An Application of NGS for Molecular Investigations in Perrault Syndrome: Study of 14 Families and Review of the Literature.

Lerat J, Jonard L, Loundon N, Christin-Maitre S, Lacombe D, Goizet C, Rouzier C, Van Maldergem L, Gherbi S, Garabedian EN, Bonnefont JP, Touraine P, Mosnier I, Munnich A, Denoyelle F, Marlin S.

Hum Mutat. 2016 Dec;37(12):1354-1362. doi: 10.1002/humu.23120. Epub 2016 Oct 7. Review.

PubMed [citation]

PMID:: 27650058

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002185752.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. This variant disrupts the p.Arg265 amino acid residue in TWNK. Other variant(s) that disrupt this residue have been observed in individuals with TWNK-related conditions (PMID: 31055809), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 694394). This missense change has been observed in individual(s) with autosomal recessive Perrault syndrome (PMID: 27650058). This variant is present in population databases (rs764669712, ExAC 0.006%). This sequence change replaces arginine with cysteine at codon 265 of the TWNK protein (p.Arg265Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine.

#	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: Nov 10, 2024

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