ClinVar Genomic variation as it relates to human health
NM_002161.6(IARS1):c.1021A>G (p.Ile341Val)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002161.6(IARS1):c.1021A>G (p.Ile341Val)
Variation ID: 2054924 Accession: VCV002054924.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q22.31 9: 92271625 (GRCh38) [ NCBI UCSC ] 9: 95033907 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 8, 2023 May 1, 2024 May 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002161.6:c.1021A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002152.2:p.Ile341Val missense NM_001374299.1:c.1021A>G NP_001361228.1:p.Ile341Val missense NM_001374300.1:c.1021A>G NP_001361229.1:p.Ile341Val missense NM_001374301.1:c.1021A>G NP_001361230.1:p.Ile341Val missense NM_001378569.1:c.1084A>G NP_001365498.1:p.Ile362Val missense NM_001378571.1:c.1042A>G NP_001365500.1:p.Ile348Val missense NM_001378572.1:c.1021A>G NP_001365501.1:p.Ile341Val missense NM_001378573.1:c.1021A>G NP_001365502.1:p.Ile341Val missense NM_001378574.1:c.1021A>G NP_001365503.1:p.Ile341Val missense NM_001378575.1:c.1021A>G NP_001365504.1:p.Ile341Val missense NM_001378576.1:c.1021A>G NP_001365505.1:p.Ile341Val missense NM_001378577.1:c.1021A>G NP_001365506.1:p.Ile341Val missense NM_001378578.1:c.1021A>G NP_001365507.1:p.Ile341Val missense NM_001378579.1:c.1021A>G NP_001365508.1:p.Ile341Val missense NM_001378580.1:c.1021A>G NP_001365509.1:p.Ile341Val missense NM_001378582.1:c.1021A>G NP_001365511.1:p.Ile341Val missense NM_001378583.1:c.898A>G NP_001365512.1:p.Ile300Val missense NM_001378584.1:c.1021A>G NP_001365513.1:p.Ile341Val missense NM_001378585.1:c.1021A>G NP_001365514.1:p.Ile341Val missense NM_001378586.1:c.1021A>G NP_001365515.1:p.Ile341Val missense NM_002161.5:c.1021A>G NM_013417.2:c.1021A>G NM_013417.4:c.1021A>G NP_038203.2:p.Ile341Val missense NR_073446.2:n.958A>G non-coding transcript variant NC_000009.12:g.92271625T>C NC_000009.11:g.95033907T>C NG_051498.1:g.27132A>G - Protein change
- I300V, I348V, I362V, I341V
- Other names
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- Canonical SPDI
- NC_000009.12:92271624:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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IARS1 | - | - |
GRCh38 GRCh38 GRCh37 |
341 | 381 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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May 18, 2023 | RCV002933073.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 18, 2021 | RCV004067059.1 |
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
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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
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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
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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. |
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Uncertain significance
(Jun 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV003262575.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 341 of the IARS protein (p.Ile341Val). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 341 of the IARS protein (p.Ile341Val). This variant is present in population databases (rs141754545, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IARS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. (less)
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Uncertain significance
(May 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003925913.1
First in ClinVar: May 27, 2023 Last updated: May 27, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
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Uncertain significance
(Oct 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV004884866.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.1021A>G (p.I341V) alteration is located in exon 11 (coding exon 10) of the IARS gene. This alteration results from a A to G substitution … (more)
The c.1021A>G (p.I341V) alteration is located in exon 11 (coding exon 10) of the IARS gene. This alteration results from a A to G substitution at nucleotide position 1021, causing the isoleucine (I) at amino acid position 341 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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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. |
Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.