VCV000618222.10 - ClinVar

NC_012920.1(MT-ND1):m.1619C>T

Germline

Top reviewed classifications are shown here.

Submission summary:

3 submissions

3 submitters

3 conditions

Reviewed by expert panel

Uncertain Significance

Jun 2023 by ClinGen Mitoch… FDA Recognized Database

for Mitochondrial disease

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_012920.1(MT-ND1):m.1619C>T

Variation ID: 618222 Accession: VCV000618222.10

Type and length

single nucleotide variant, 1 bp

Location

MT: 1619 (GRCh38) [ NCBI UCSC ] MT: 1619 (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	Feb 18, 2019	Aug 18, 2024	Jun 26, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_012920.1:m.1619C>T

Protein change

Other names

Canonical SPDI

NC_012920.1:1618: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.

Links

dbSNP: rs1569483811 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.
MT-TV		-	-	GRCh38	32	33

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.
not provided	Uncertain significance (1)	criteria provided, single submitter	Jul 18, 2017	RCV000756364.8
Mitochondrial disease	Uncertain significance (1)	reviewed by expert panel	Jun 26, 2023	RCV004691292.1
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke	Likely benign (1)	criteria provided, single submitter	Jul 12, 2019	RCV000850665.1

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.
Uncertain Significance (Jun 26, 2023)	reviewed by expert panel (clingen mito disease acmg specifications v1-1) Method: curation	Mitochondrial disease (Mitochondrial inheritance) Affected status: unknown Allele origin: germline	ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen FDA Recognized Database Accession: SCV005187325.1 First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/586e314d-379b-4960-bd74-ccfddd8d533c Comment: The m.1619C>T variant in MT-TV has been reported in one individual in the medical literature, however no clinical details are provided (PMID: 31965079). There are … (more) The m.1619C>T variant in MT-TV has been reported in one individual in the medical literature, however no clinical details are provided (PMID: 31965079). There are no reported de novo occurrences of this variant to our knowledge. There are no reports of large families with this variant segregating with disease manifestations. This variant is present in population databases (Mitomap's 3/59,389 sequences: AF=0.005%; Helix's 24/195,983 sequences: AF=0.055%; and gnomAD v3.1.2: AF=0.005% including three homoplasmic occurrences). The computational predictor MitoTIP suggests this variant is benign (15.2 percentile) and HmtVAR (score 0) predicts it to be polymorphic (BP4). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on June 26, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4. (less)
Uncertain significance (Jul 18, 2017)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000884156.1 First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019	Comment: This variant affects the mitochondrial tRNA for valine and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor … (more) This variant affects the mitochondrial tRNA for valine and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also rare in population databases such as MITOMAP (0.005% population frequency). However, the cytosine at position 1619 is weakly conserved (UCSC genome browser), suggesting this variant is evolutionary tolerated. However, based on the available information, the clinical significance of the m.1619C>T variant cannot be determined with certainty. (less)
Likely benign (Jul 12, 2019)	criteria provided, single submitter (Modified ACMG Guidelines (Unpublished)) Method: clinical testing	Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Affected status: unknown Allele origin: germline	Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine Accession: SCV000992896.1 First in ClinVar: Sep 22, 2019 Last updated: Sep 22, 2019	Publications: PubMed (1) PubMed: 31965079 Comment: The NC_012920.1:m.1619C>T variant in MT-TV gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the … (more) The NC_012920.1:m.1619C>T variant in MT-TV gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BP5, BP4 (less)

Comment:

The m.1619C>T variant in MT-TV has been reported in one individual in the medical literature, however no clinical details are provided (PMID: 31965079). There are no reported de novo occurrences of this variant to our knowledge. There are no reports of large families with this variant segregating with disease manifestations. This variant is present in population databases (Mitomap's 3/59,389 sequences: AF=0.005%; Helix's 24/195,983 sequences: AF=0.055%; and gnomAD v3.1.2: AF=0.005% including three homoplasmic occurrences). The computational predictor MitoTIP suggests this variant is benign (15.2 percentile) and HmtVAR (score 0) predicts it to be polymorphic (BP4). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on June 26, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4.

Comment:

This variant affects the mitochondrial tRNA for valine and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also rare in population databases such as MITOMAP (0.005% population frequency). However, the cytosine at position 1619 is weakly conserved (UCSC genome browser), suggesting this variant is evolutionary tolerated. However, based on the available information, the clinical significance of the m.1619C>T variant cannot be determined with certainty.

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
Interpretation of mitochondrial tRNA variants.	Wong LC	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 31965079
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/586e314d-379b-4960-bd74-ccfddd8d533c	-	-	-	-

Text-mined citations for rs1569483811 ...

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 Aug 25, 2024

ClinVar Genomic variation as it relates to human health

NC_012920.1(MT-ND1):m.1619C>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1569483811 ...