ClinVar Genomic variation as it relates to human health
NM_007078.3(LDB3):c.818G>A (p.Arg273His)
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_007078.3(LDB3):c.818G>A (p.Arg273His)
Variation ID: 880174 Accession: VCV000880174.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86692024 (GRCh38) [ NCBI UCSC ] 10: 88451781 (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 May 31, 2020 Feb 14, 2024 Nov 20, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007078.3:c.818G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009009.1:p.Arg273His missense NM_001368067.1:c.677G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001354996.1:p.Arg226His missense NM_001080114.2:c.677G>A NP_001073583.1:p.Arg226His missense NM_001080115.2:c.818G>A NP_001073584.1:p.Arg273His missense NM_001080116.1:c.677G>A NP_001073585.1:p.Arg226His missense NM_001171610.2:c.1022G>A NP_001165081.1:p.Arg341His missense NM_001171611.2:c.1022G>A NP_001165082.1:p.Arg341His missense NM_001368063.1:c.818G>A NP_001354992.1:p.Arg273His missense NM_001368064.1:c.818G>A NP_001354993.1:p.Arg273His missense NM_001368065.1:c.818G>A NP_001354994.1:p.Arg273His missense NM_001368066.1:c.677G>A NP_001354995.1:p.Arg226His missense NM_001368068.1:c.677G>A NP_001354997.1:p.Arg226His missense NM_007078.2:c.818G>A NC_000010.11:g.86692024G>A NC_000010.10:g.88451781G>A NG_008876.1:g.28461G>A LRG_385:g.28461G>A LRG_385t2:c.677G>A LRG_385p2:p.Arg226His - Protein change
- R341H, R273H, R226H
- Other names
- p.Arg273His
- Canonical SPDI
- NC_000010.11:86692023:G:A
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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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
- 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
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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LDB3 | - | - |
GRCh38 GRCh37 |
1168 | 1347 |
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
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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 (1) |
criteria provided, single submitter
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Jan 12, 2018 | RCV001108265.4 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Nov 20, 2023 | RCV001108264.11 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 25, 2022 | RCV002429758.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 16, 2021 | RCV002489756.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Nov 23, 2022 | RCV003480959.1 |
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. |
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Myofibrillar myopathy 4
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001265485.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Observation 1: Observation 2: |
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Uncertain significance
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1C
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001265486.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Observation 1: Observation 2: |
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Uncertain significance
(Aug 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002679656.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.R273H variant (also known as c.818G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide … (more)
The p.R273H variant (also known as c.818G>A), located in coding exon 5 of the LDB3 gene, results from a G to A substitution at nucleotide position 818. This variant (described as p.R341H) was detected in a dilated cardiomyopathy cohort; however, clinical details were limited (Haas J et al. Eur. Heart J., 2015 May;36:1123-35a). The arginine at codon 273 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Aug 16, 2021)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1C
Myofibrillar myopathy 4
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002775453.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Nov 23, 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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV004225284.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Number of individuals with the variant: 2
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Uncertain significance
(Nov 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Myofibrillar myopathy 4
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001385418.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 226 of the LDB3 protein (p.Arg226His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 226 of the LDB3 protein (p.Arg226His). This variant is present in population databases (rs763481542, gnomAD 0.006%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 25163546). This variant is also known as NM_001171611:c.1022G>A (p.Arg341His). ClinVar contains an entry for this variant (Variation ID: 880174). 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. (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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Atlas of the clinical genetics of human dilated cardiomyopathy. | Haas J | European heart journal | 2015 | PMID: 25163546 |
Text-mined citations for rs763481542 ...
HelpRecord last updated Feb 20, 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.