ClinVar Genomic variation as it relates to human health
NM_001386795.1(DTNA):c.177A>G (p.Ile59Met)
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.
Likely pathogenic(2); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001386795.1(DTNA):c.177A>G (p.Ile59Met)
Variation ID: 374197 Accession: VCV000374197.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q12.1 18: 34794065 (GRCh38) [ NCBI UCSC ] 18: 32374029 (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 Jan 13, 2017 Feb 20, 2024 Sep 13, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001386795.1:c.177A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001373724.1:p.Ile59Met missense NM_001128175.2:c.177A>G NP_001121647.1:p.Ile59Met missense NM_001198938.2:c.177A>G NP_001185867.1:p.Ile59Met missense NM_001198939.2:c.177A>G NP_001185868.1:p.Ile59Met missense NM_001198940.2:c.177A>G NP_001185869.1:p.Ile59Met missense NM_001198941.2:c.177A>G NP_001185870.1:p.Ile59Met missense NM_001198945.2:c.177A>G NP_001185874.1:p.Ile59Met missense NM_001386753.1:c.177A>G NP_001373682.1:p.Ile59Met missense NM_001386754.1:c.177A>G NP_001373683.1:p.Ile59Met missense NM_001386755.1:c.177A>G NP_001373684.1:p.Ile59Met missense NM_001386756.1:c.177A>G NP_001373685.1:p.Ile59Met missense NM_001386757.1:c.177A>G NP_001373686.1:p.Ile59Met missense NM_001386758.1:c.177A>G NP_001373687.1:p.Ile59Met missense NM_001386759.1:c.177A>G NP_001373688.1:p.Ile59Met missense NM_001386760.1:c.177A>G NP_001373689.1:p.Ile59Met missense NM_001386761.1:c.177A>G NP_001373690.1:p.Ile59Met missense NM_001386762.1:c.177A>G NP_001373691.1:p.Ile59Met missense NM_001386763.1:c.177A>G NP_001373692.1:p.Ile59Met missense NM_001386764.1:c.177A>G NP_001373693.1:p.Ile59Met missense NM_001386765.1:c.177A>G NP_001373694.1:p.Ile59Met missense NM_001386766.1:c.177A>G NP_001373695.1:p.Ile59Met missense NM_001386767.1:c.177A>G NP_001373696.1:p.Ile59Met missense NM_001386768.1:c.177A>G NP_001373697.1:p.Ile59Met missense NM_001386769.1:c.177A>G NP_001373698.1:p.Ile59Met missense NM_001386770.1:c.177A>G NP_001373699.1:p.Ile59Met missense NM_001386771.1:c.177A>G NP_001373700.1:p.Ile59Met missense NM_001386772.1:c.177A>G NP_001373701.1:p.Ile59Met missense NM_001386773.1:c.177A>G NP_001373702.1:p.Ile59Met missense NM_001386774.1:c.177A>G NP_001373703.1:p.Ile59Met missense NM_001386775.1:c.177A>G NP_001373704.1:p.Ile59Met missense NM_001386776.1:c.177A>G NP_001373705.1:p.Ile59Met missense NM_001386777.1:c.177A>G NP_001373706.1:p.Ile59Met missense NM_001386788.1:c.177A>G NP_001373717.1:p.Ile59Met missense NM_001390.5:c.177A>G NP_001381.2:p.Ile59Met missense NM_001391.5:c.177A>G NP_001382.2:p.Ile59Met missense NM_001392.5:c.177A>G NP_001383.2:p.Ile59Met missense NM_032975.4:c.177A>G NP_116757.2:p.Ile59Met missense NM_032978.7:c.177A>G NP_116760.2:p.Ile59Met missense NM_032979.5:c.177A>G NP_116761.2:p.Ile59Met missense NC_000018.10:g.34794065A>G NC_000018.9:g.32374029A>G NG_009201.1:g.305776A>G LRG_756:g.305776A>G LRG_756t1:c.177A>G LRG_756p1:p.Ile59Met LRG_756t2:c.177A>G LRG_756p2:p.Ile59Met LRG_756t3:c.177A>G LRG_756p3:p.Ile59Met LRG_756t4:c.177A>G LRG_756p4:p.Ile59Met - Protein change
- I59M
- Other names
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- Canonical SPDI
- NC_000018.10:34794064:A:G
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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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
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
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. |
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DTNA | - | - |
GRCh38 GRCh37 |
609 | 651 |
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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Dec 13, 2013 | RCV000415295.2 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Sep 13, 2019 | RCV001214045.10 |
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. |
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Likely pathogenic
(Dec 13, 2013)
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criteria provided, single submitter
Method: clinical testing
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Cardiac arrhythmia
Noncompaction cardiomyopathy
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000493035.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
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Likely pathogenic
(Jan 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Left ventricular noncompaction 1
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368765.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Likely pathogenic.
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Uncertain significance
(Sep 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Left ventricular noncompaction 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001385708.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
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 … (more)
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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 374197). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 59 of the DTNA protein (p.Ile59Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. (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
HelpTitle | Author | Journal | Year | Link |
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LOVD v.2.0: the next generation in gene variant databases. | Fokkema IF | Human mutation | 2011 | PMID: 21520333 |
Text-mined citations for rs1057518968 ...
HelpRecord last updated Feb 28, 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.