VCV000141427.44 - ClinVar

NM_020442.6(VARS2):c.1010C>T (p.Thr337Ile)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(12)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020442.6(VARS2):c.1010C>T (p.Thr337Ile)

Variation ID: 141427 Accession: VCV000141427.44

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6p21.33 6: 30918851 (GRCh38) [ NCBI UCSC ] 6: 30886628 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	May 19, 2015	Oct 20, 2024	Jan 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_020442.6:c.1010C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_065175.4:p.Thr337Ile	missense
NM_001167733.3:c.590C>T	NP_001161205.1:p.Thr197Ile	missense
NM_001167734.2:c.1100C>T	NP_001161206.1:p.Thr367Ile	missense
NM_020442.5:c.1010C>T
NC_000006.12:g.30918851C>T
NC_000006.11:g.30886628C>T
NG_034224.1:g.9644C>T

... more HGVS ... less HGVS

Protein change

T367I, T337I, T197I

Other names

Canonical SPDI

NC_000006.12:30918850:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00002

Exome Aggregation Consortium (ExAC) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00006

Links

dbSNP: rs587777585 ClinGen: CA215019 OMIM: 612802.0003 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
VARS2		-	-	GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh38 GRCh37	407	504

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Combined oxidative phosphorylation defect type 20	Pathogenic (8)	criteria provided, multiple submitters, no conflicts	Jun 26, 2023	RCV000129937.25
Inborn genetic diseases	Pathogenic (1)	criteria provided, single submitter	Dec 31, 2014	RCV000623604.10
not provided	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jan 5, 2024	RCV001090482.36

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001137064.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Pathogenic (Oct 22, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: yes Allele origin: germline	MGZ Medical Genetics Center Accession: SCV002579561.1 First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 Comment: ACMG criteria applied: PM3_VSTR, PS4_MOD, PM2_SUP, PP3	Number of individuals with the variant: 1 Sex: female
Pathogenic (Dec 31, 2014)	criteria provided, single submitter (Ambry exome assertion method (8-5-2015)) Method: clinical testing	Inborn genetic diseases Affected status: yes Allele origin: germline	Ambry Genetics Accession: SCV000740809.3 First in ClinVar: Apr 15, 2018 Last updated: Jan 07, 2023	Publications: PubMed (1) PubMed: 12345 Number of individuals with the variant: 1 Clinical Features: Global developmental delay (present) , Movement disorder (present) , Athetosis (present) , Dystonia (present) , Growth delay (present) , Esotropia (present) , Nystagmus (present) , … (more) Global developmental delay (present) , Movement disorder (present) , Athetosis (present) , Dystonia (present) , Growth delay (present) , Esotropia (present) , Nystagmus (present) , Gastroesophageal reflux (present) , Feeding difficulties (present) , Vesicoureteral reflux (present) , Neurogenic bladder (present) , Muscular hypotonia (present) , Conductive hearing impairment (present) , Telecanthus (present) , Epicanthus (present) , Anteverted nares (present) , Thick vermilion border (present) , Downturned corners of mouth (present) (less) Sex: female Ethnicity/Population group: Caucasian
Pathogenic (May 24, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001764381.2 First in ClinVar: Aug 07, 2021 Last updated: Jun 03, 2023	Comment: Published functional studies in yeast suggest that T367I could result in an OXPHOS-dependent growth defect, with a slightly lower respiration rate in mutants than in … (more) Published functional studies in yeast suggest that T367I could result in an OXPHOS-dependent growth defect, with a slightly lower respiration rate in mutants than in wildtype strain (Diodato et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24827421, 29478218, 27502409, 29314548, 30458719, 31623496, 34426522, 27290639, 30925032, 31064326) (less)
Pathogenic (Jun 26, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV004021167.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Publications: PubMed (4) PubMed: 27290639‚ 34362006‚ 27502409‚ 24639874 Comment: Variant summary: VARS2 c.1010C>T (p.Thr337Ile) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Aminoacyl-tRNA synthetase, class Ia … (more) Variant summary: VARS2 c.1010C>T (p.Thr337Ile) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Aminoacyl-tRNA synthetase, class Ia (IPR002300) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 246604 control chromosomes (gnomAD). c.1010C>T has been reported in the literature in multiple individuals affected with mitochondrial disorders (Pronicka_2016, Diodato_2014, Tolomeo_2021, Baertling_2017), including in a compound heterozygous patient with a likely pathogenic variant in trans. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function in a yeast model, finding that yeast culture carrying the variant in the orthologous residue had a slower growth rate (Diodato_2014). The following publications have been ascertained in the context of this evaluation (PMID: 27290639, 24639874, 34362006, 27502409). Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Jan 05, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002243757.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024	Publications: PubMed (6) PubMed: 24827421‚ 27290639‚ 27502409‚ 29314548‚ 31064326‚ 31623496 Comment: This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 367 of the VARS2 protein (p.Thr367Ile). … (more) This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 367 of the VARS2 protein (p.Thr367Ile). This variant is present in population databases (rs587777585, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of VARS2-related conditions (PMID: 24827421, 27290639, 27502409, 29314548, 31064326, 31623496). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 141427). 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 expected to disrupt VARS2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects VARS2 function (PMID: 24827421). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Feb 01, 2020)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001246055.26 First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024	Number of individuals with the variant: 2
Pathogenic (Nov 16, 2017)	criteria provided, single submitter (Classification criteria August 2017) Method: clinical testing	Combined oxidative phosphorylation defect type 20 (Autosomal recessive inheritance) Affected status: yes Allele origin: maternal	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München Accession: SCV000680430.1 First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018	Publications: PubMed (1) PubMed: 27502409 Sex: male Tissue: blood
Pathogenic (May 22, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: yes Allele origin: germline	3billion Accession: SCV002521733.1 First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022	Publications: PubMed (1) PubMed: 24827421 Comment: The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Missense changes are a common disease-causing mechanism. … (more) The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Missense changes are a common disease-causing mechanism. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:24827421). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.93). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000141427). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less) Clinical Features: Hypertelorism (present) , Broad forehead (present) , Generalized hypotonia (present) , Global developmental delay (present) , Myoclonus (present) , Encephalopathy (present) , Seizure (present) , … (more) Hypertelorism (present) , Broad forehead (present) , Generalized hypotonia (present) , Global developmental delay (present) , Myoclonus (present) , Encephalopathy (present) , Seizure (present) , Motor delay (present) , Cerebellar atrophy (present) , Hypertrophic cardiomyopathy (present) (less)
Pathogenic (Jun 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: yes Allele origin: germline	DASA Accession: SCV002526415.1 First in ClinVar: Jun 18, 2022 Last updated: Jun 18, 2022	Publications: PubMed (9) PubMed: 24827421‚ 27290639‚ 27502409‚ 29314548‚ 29478218‚ 30458719‚ 30925032‚ 31064326‚ 31623496 Comment: The c.1100C>T;p.(Thr367Ile) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 141427; PMID: 24827421; 27290639; 27502409; … (more) The c.1100C>T;p.(Thr367Ile) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 141427; PMID: 24827421; 27290639; 27502409; 29314548; 29478218; 30458719; 30925032; 31064326; 31623496) - .PS4.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 24827421) - PS3_supporting. The variant is present at low allele frequencies population databases (rs587777585– gnomAD 0.0002628%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The p.(Thr367Ile) was detected in trans with a Pathogenic variant (PMID: 29314548; 29478218; 30458719; 31064326; 31623496) - PM3_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is Pathogenic (less) Number of individuals with the variant: 2 Sex: mixed Geographic origin: Brazil
Pathogenic (Jul 25, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Combined oxidative phosphorylation defect type 20 Affected status: yes Allele origin: germline	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV003807337.1 First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023	Comment: ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PM3 strong, PP3 supporting Number of individuals with the variant: 1 Clinical Features: Severe failure to thrive (present) , Decreased body weight (present) , Mild global developmental delay (present) , Neonatal hypoglycemia (present) , Abnormality of amino acid … (more) Severe failure to thrive (present) , Decreased body weight (present) , Mild global developmental delay (present) , Neonatal hypoglycemia (present) , Abnormality of amino acid metabolism (present) , Small for gestational age (present) , Nausea and vomiting (present) , Short stature (present) , Global developmental delay (present) , Failure to thrive (present) (less) Geographic origin: Brazil Method: Paired-end whole-genome sequencing
Pathogenic (Aug 01, 2014)	no assertion criteria provided Method: literature only	COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 20 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000184756.3 First in ClinVar: Aug 06, 2014 Last updated: Jul 16, 2020	Publications: PubMed (4) PubMed: 24827421‚ 27502409‚ 29314548‚ 31064326 Comment on evidence: In a boy with combined oxidative phosphorylation deficiency-20 (COXPD20; 615917) manifest as mitochondrial encephalomyopathy, Diodato et al. (2014) identified a homozygous c.1100C-T transition in the … (more) In a boy with combined oxidative phosphorylation deficiency-20 (COXPD20; 615917) manifest as mitochondrial encephalomyopathy, Diodato et al. (2014) identified a homozygous c.1100C-T transition in the VARS2 gene, resulting in a thr367-to-ile (T367I) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not present in public databases, including dbSNP and the Exome Sequencing Project. Western blot analysis of patient fibroblasts showed decreased levels of the VARS2 protein, suggesting partial instability, and charged tRNA-Val was also decreased compared to controls. Studies of the homologous mutant in yeast were consistent with decreased respiration, possibly due to interruption of the substrate-binding site by the substitution. Introduction of wildtype VARS2 rescued the defective mitochondrial respiration observed in patient fibroblasts. In a Greek infant with COXPD20, Baertling et al. (2017) identified compound heterozygous mutations in the VARS2 gene: T367I and a c.601C-T transition resulting in an arg201-to-trp (R201W; 612802.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. In the ExAC database, the T367I variant had a frequency of 0.0024% and the R201W variant a frequency of 0.0025%. Studies in patient fibroblasts showed decreased VARS2 protein levels and decreased oxygen consumption. In a girl (P1) from a Polish family (family 1) and in 3 sibs (P11, P12, P13) from an Afghan family (family 9) with COXPD20, Bruni et al. (2018) identified homozygosity for the recurrent T367I mutation in the VARS2 gene. The mutation occurs in a region important for the interaction of VARS2 with the cognate tRNA. Bruni et al. (2018) also found the T367I variant in compound heterozygous state in 5 additional patients (see, e.g., 612802.0007, 612802.0008, 612802.0009). In 2 unrelated girls from Sardinia with COXPD20, Begliuomini et al. (2019) identified homozygosity for the T367I mutation in the VARS2 gene. The mutations were identified by whole-exome sequencing or sequencing of a targeted mitochondrial panel and confirmed by Sanger sequencing. The parents of 1 girl were noted to be heterozygous for the mutation. A skeletal muscle biopsy in 1 patient showed partial reduction of respiratory chain complexes I+III. (less)
click to load more click to collapse

Comment:

Published functional studies in yeast suggest that T367I could result in an OXPHOS-dependent growth defect, with a slightly lower respiration rate in mutants than in wildtype strain (Diodato et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24827421, 29478218, 27502409, 29314548, 30458719, 31623496, 34426522, 27290639, 30925032, 31064326)

Comment:

Variant summary: VARS2 c.1010C>T (p.Thr337Ile) results in a non-conservative amino acid change to a highly conserved residue (HGMD) located in the Aminoacyl-tRNA synthetase, class Ia (IPR002300) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 246604 control chromosomes (gnomAD). c.1010C>T has been reported in the literature in multiple individuals affected with mitochondrial disorders (Pronicka_2016, Diodato_2014, Tolomeo_2021, Baertling_2017), including in a compound heterozygous patient with a likely pathogenic variant in trans. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function in a yeast model, finding that yeast culture carrying the variant in the orthologous residue had a slower growth rate (Diodato_2014). The following publications have been ascertained in the context of this evaluation (PMID: 27290639, 24639874, 34362006, 27502409). Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 367 of the VARS2 protein (p.Thr367Ile). This variant is present in population databases (rs587777585, gnomAD 0.009%). This missense change has been observed in individual(s) with clinical features of VARS2-related conditions (PMID: 24827421, 27290639, 27502409, 29314548, 31064326, 31623496). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 141427). 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 expected to disrupt VARS2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects VARS2 function (PMID: 24827421). For these reasons, this variant has been classified as Pathogenic.

Comment:

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). Missense changes are a common disease-causing mechanism. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:24827421). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.91; 3Cnet: 0.93). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000141427). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

Comment:

The c.1100C>T;p.(Thr367Ile) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 141427; PMID: 24827421; 27290639; 27502409; 29314548; 29478218; 30458719; 30925032; 31064326; 31623496) - .PS4.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 24827421) - PS3_supporting. The variant is present at low allele frequencies population databases (rs587777585– gnomAD 0.0002628%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The p.(Thr367Ile) was detected in trans with a Pathogenic variant (PMID: 29314548; 29478218; 30458719; 31064326; 31623496) - PM3_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is Pathogenic

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The Diagnostic Approach to Mitochondrial Disorders in Children in the Era of Next-Generation Sequencing: A 4-Year Cohort Study.	Tolomeo D	Journal of clinical medicine	2021	PMID: 34362006
A novel VARS2 gene variant in a patient with epileptic encephalopathy.	Ruzman L	Upsala journal of medical sciences	2019	PMID: 31623496
VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype.	Begliuomini C	BMC medical genetics	2019	PMID: 31064326
The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies.	Abu Diab A	Acta ophthalmologica	2019	PMID: 30925032
A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.	Ma K	BMC medical genetics	2018	PMID: 30458719
Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant.	Pereira S	JIMD reports	2018	PMID: 29478218
Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease.	Bruni F	Human mutation	2018	PMID: 29314548
Neonatal encephalocardiomyopathy caused by mutations in VARS2.	Baertling F	Metabolic brain disease	2017	PMID: 27502409
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.	Pronicka E	Journal of translational medicine	2016	PMID: 27290639
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.	Diodato D	Human mutation	2014	PMID: 24827421
The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes.	Diodato D	International journal of cell biology	2014	PMID: 24639874
A new granulation method for compressed tablets [proceedings].	Rubinstein MH	The Journal of pharmacy and pharmacology	1976	PMID: 12345
click to load more click to collapse

Text-mined citations for rs587777585 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_020442.6(VARS2):c.1010C>T (p.Thr337Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs587777585 ...