NM_021830.5(TWNK):c.241C>G (p.Leu81Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jun 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000320273.27

Allele description [Variation Report for NM_021830.5(TWNK):c.241C>G (p.Leu81Val)]

NM_021830.5(TWNK):c.241C>G (p.Leu81Val)

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.241C>G (p.Leu81Val)

HGVS:

NC_000010.11:g.100988451C>G
NG_011646.1:g.4065G>C
NG_012624.1:g.5916C>G
NM_001163812.2:c.241C>G
NM_001163813.2:c.-120+838C>G
NM_001163814.2:c.-120+838C>G
NM_001368275.1:c.-58+838C>G
NM_021830.5:c.241C>GMANE SELECT
NP_001157284.1:p.Leu81Val
NP_068602.2:p.Leu81Val
NC_000010.10:g.102748208C>G
NM_021830.4:c.241C>G
NR_160738.1:n.909C>G
NR_160740.1:n.909C>G
NR_160741.1:n.909C>G
NR_160742.1:n.909C>G
p.Leu81Val

Protein change:

L81V

Links:

dbSNP: rs145068570

NCBI 1000 Genomes Browser:

rs145068570

Molecular consequence:

NM_001163813.2:c.-120+838C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001163814.2:c.-120+838C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001368275.1:c.-58+838C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001163812.2:c.241C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021830.5:c.241C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_160738.1:n.909C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160740.1:n.909C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160741.1:n.909C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_160742.1:n.909C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

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
SCV000329171	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 3, 2023)	germline	clinical testing	Citation Link,
SCV001714361	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 19, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002343020	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 25, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002585247	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

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 GeneDx, SCV000329171.8

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

Description

Observed in patient with possible mitochondrial disease in published literature; however, no further information was provided (Davis et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31266935, 35641312)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714361.1

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

#	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

From Invitae, SCV002343020.3

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

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV002585247.13

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

Description

TWNK: PM2:Supporting, PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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