ClinVar contains an entry for this variant (Variation ID: 623092). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 29118297). This variant is present in population databases (rs775975702, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 49 of the DTNA protein (p.Asn49Ser). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. Experimental studies have shown that this missense change affects DTNA function (PMID: 29118297).
ClinVar Genomic variation as it relates to human health
NM_001386795.1(DTNA):c.146A>G (p.Asn49Ser)
Germline
Classification
Help
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.
(2)
Help
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.
Uncertain significance
2
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001386795.1(DTNA):c.146A>G (p.Asn49Ser)
Variation ID: 623092 Accession: VCV000623092.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q12.1 18: 34766039 (GRCh38) [ NCBI UCSC ] 18: 32346003 (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 Mar 25, 2019 Feb 20, 2024 Jun 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001386795.1:c.146A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001373724.1:p.Asn49Ser missense NM_001128175.2:c.146A>G NP_001121647.1:p.Asn49Ser missense NM_001198938.2:c.146A>G NP_001185867.1:p.Asn49Ser missense NM_001198939.2:c.146A>G NP_001185868.1:p.Asn49Ser missense NM_001198940.2:c.146A>G NP_001185869.1:p.Asn49Ser missense NM_001198941.2:c.146A>G NP_001185870.1:p.Asn49Ser missense NM_001198945.2:c.146A>G NP_001185874.1:p.Asn49Ser missense NM_001386753.1:c.146A>G NP_001373682.1:p.Asn49Ser missense NM_001386754.1:c.146A>G NP_001373683.1:p.Asn49Ser missense NM_001386755.1:c.146A>G NP_001373684.1:p.Asn49Ser missense NM_001386756.1:c.146A>G NP_001373685.1:p.Asn49Ser missense NM_001386757.1:c.146A>G NP_001373686.1:p.Asn49Ser missense NM_001386758.1:c.146A>G NP_001373687.1:p.Asn49Ser missense NM_001386759.1:c.146A>G NP_001373688.1:p.Asn49Ser missense NM_001386760.1:c.146A>G NP_001373689.1:p.Asn49Ser missense NM_001386761.1:c.146A>G NP_001373690.1:p.Asn49Ser missense NM_001386762.1:c.146A>G NP_001373691.1:p.Asn49Ser missense NM_001386763.1:c.146A>G NP_001373692.1:p.Asn49Ser missense NM_001386764.1:c.146A>G NP_001373693.1:p.Asn49Ser missense NM_001386765.1:c.146A>G NP_001373694.1:p.Asn49Ser missense NM_001386766.1:c.146A>G NP_001373695.1:p.Asn49Ser missense NM_001386767.1:c.146A>G NP_001373696.1:p.Asn49Ser missense NM_001386768.1:c.146A>G NP_001373697.1:p.Asn49Ser missense NM_001386769.1:c.146A>G NP_001373698.1:p.Asn49Ser missense NM_001386770.1:c.146A>G NP_001373699.1:p.Asn49Ser missense NM_001386771.1:c.146A>G NP_001373700.1:p.Asn49Ser missense NM_001386772.1:c.146A>G NP_001373701.1:p.Asn49Ser missense NM_001386773.1:c.146A>G NP_001373702.1:p.Asn49Ser missense NM_001386774.1:c.146A>G NP_001373703.1:p.Asn49Ser missense NM_001386775.1:c.146A>G NP_001373704.1:p.Asn49Ser missense NM_001386776.1:c.146A>G NP_001373705.1:p.Asn49Ser missense NM_001386777.1:c.146A>G NP_001373706.1:p.Asn49Ser missense NM_001386788.1:c.146A>G NP_001373717.1:p.Asn49Ser missense NM_001390.5:c.146A>G NP_001381.2:p.Asn49Ser missense NM_001391.5:c.146A>G NP_001382.2:p.Asn49Ser missense NM_001392.5:c.146A>G NP_001383.2:p.Asn49Ser missense NM_032975.4:c.146A>G NP_116757.2:p.Asn49Ser missense NM_032978.7:c.146A>G NP_116760.2:p.Asn49Ser missense NM_032979.5:c.146A>G NP_116761.2:p.Asn49Ser missense NC_000018.10:g.34766039A>G NC_000018.9:g.32346003A>G NG_009201.1:g.277750A>G LRG_756:g.277750A>G LRG_756t1:c.146A>G LRG_756p1:p.Asn49Ser LRG_756t2:c.146A>G LRG_756p2:p.Asn49Ser LRG_756t3:c.146A>G LRG_756p3:p.Asn49Ser LRG_756t4:c.146A>G LRG_756p4:p.Asn49Ser - Protein change
- N49S
- Other names
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- Canonical SPDI
- NC_000018.10:34766038: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.
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The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
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| DTNA | - | - |
GRCh38 GRCh37 |
615 | 657 | |
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. |
|---|---|---|---|---|
| Uncertain significance (2) |
criteria provided, single submitter
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Jun 19, 2023 | RCV000761211.3 |
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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|---|---|---|---|---|---|
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Uncertain significance
(Jun 19, 2023)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004521609.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 623092). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 29118297). … (more)
ClinVar contains an entry for this variant (Variation ID: 623092). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 29118297). This variant is present in population databases (rs775975702, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 49 of the DTNA protein (p.Asn49Ser). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. Experimental studies have shown that this missense change affects DTNA function (PMID: 29118297). (less)
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Pathogenic
(Mar 18, 2019)
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no assertion criteria provided
Method: literature only
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LEFT VENTRICULAR NONCOMPACTION 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000891164.1
First in ClinVar: Mar 25, 2019 Last updated: Mar 25, 2019 |
Comment on evidence:
In a 39-year-old man with a diagnosis of left ventricular noncompaction (LVNC1; 604169), in whom mutations in 8 candidate genes were excluded, Cao et al. … (more)
In a 39-year-old man with a diagnosis of left ventricular noncompaction (LVNC1; 604169), in whom mutations in 8 candidate genes were excluded, Cao et al. (2017) identified a heterozygous c.146A-G transition in the DTNA gene, resulting in an asn49-to-ser (N49S) substitution at a highly conserved residue in the WW domain. The mutation was not found in the NHLBI ESP or 1000 Genomes Project databases or in 400 ethnically matched controls. A cardiac-specific transgenic mouse model that overexpressed Dtna with the N49S mutation was found to have a progressive cardiomyopathy characterized by dilated and thinner LV, cardiac systolic dysfunction, and age-related LV hypertrabeculation. (less)
|
Comment:
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:
ClinVar contains an entry for this variant (Variation ID: 623092). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 29118297). This variant is present in population databases (rs775975702, gnomAD 0.0009%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 49 of the DTNA protein (p.Asn49Ser). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. Experimental studies have shown that this missense change affects DTNA function (PMID: 29118297).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Phenotype and Functional Analyses in a Transgenic Mouse Model of Left Ventricular Noncompaction Caused by a DTNA Mutation. | Cao Q | International heart journal | 2017 | PMID: 29118297 |
Text-mined citations for rs775975702 ...
HelpThese 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 Sep 29, 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.