ClinVar Genomic variation as it relates to human health
NM_007078.3(LDB3):c.1672A>G (p.Ile558Val)
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.
Uncertain significance(1); Benign(4); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007078.3(LDB3):c.1672A>G (p.Ile558Val)
Variation ID: 45532 Accession: VCV000045532.28
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86716767 (GRCh38) [ NCBI UCSC ] 10: 88476524 (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 Jun 8, 2015 May 1, 2024 Dec 11, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007078.3:c.1672A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009009.1:p.Ile558Val missense NM_001080114.2:c.1342A>G NP_001073583.1:p.Ile448Val missense NM_001171610.2:c.1687A>G NP_001165081.1:p.Ile563Val missense NM_001368064.1:c.1483A>G NP_001354993.1:p.Ile495Val missense NM_001368065.1:c.1483A>G NP_001354994.1:p.Ile495Val missense NM_001368066.1:c.1531A>G NP_001354995.1:p.Ile511Val missense NC_000010.11:g.86716767A>G NC_000010.10:g.88476524A>G NG_008876.1:g.53204A>G LRG_385:g.53204A>G LRG_385t1:c.1672A>G LRG_385p1:p.Ile558Val - Protein change
- I558V, I448V, I511V, I495V, I563V
- Other names
- p.I558V:ATC>GTC
- Canonical SPDI
- NC_000010.11:86716766: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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0.00060 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00003
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00028
1000 Genomes Project 30x 0.00047
1000 Genomes Project 0.00060
Exome Aggregation Consortium (ExAC) 0.00060
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 |
1186 | 1365 |
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. |
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Likely benign (1) |
criteria provided, single submitter
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Jun 11, 2015 | RCV000038741.16 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Apr 1, 2023 | RCV000171998.24 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 18, 2019 | RCV000852622.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Dec 11, 2023 | RCV000988404.15 | |
Benign (1) |
criteria provided, single submitter
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Nov 30, 2017 | RCV001170179.10 | |
Likely benign (1) |
criteria provided, single submitter
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Sep 3, 2020 | RCV002399380.9 |
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
(Jun 24, 2013)
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criteria provided, single submitter
Method: research
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Not provided
Affected status: unknown
Allele origin:
unknown
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000054757.1 First in ClinVar: Jun 08, 2015 Last updated: Jun 08, 2015
Comments (2):
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less)
Medical sequencing
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Number of individuals with the variant: 1
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Likely benign
(Jun 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000062419.4
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
p.Ile558Val in exon 9 of LDB3: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (40/12734) South … (more)
p.Ile558Val in exon 9 of LDB3: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (40/12734) South Asian chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs372331627). (less)
Number of individuals with the variant: 3
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Benign
(Nov 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Cardiomyopathy
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV001332729.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
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Benign
(Sep 30, 2020)
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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: SCV000236009.9
First in ClinVar: Jan 31, 2015 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 25179549, 24503780, 26112015, 27896284, 20474083, 25351510, 27633507, 27884173, 30315573, 31127727)
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Likely benign
(Mar 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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Arrhythmogenic right ventricular cardiomyopathy
Affected status: yes
Allele origin:
germline
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Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego
Accession: SCV000995326.1
First in ClinVar: Oct 12, 2019 Last updated: Oct 12, 2019 |
Number of individuals with the variant: 1
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Benign
(Aug 22, 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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Mendelics
Accession: SCV001138109.2
First in ClinVar: Jan 09, 2020 Last updated: Aug 25, 2023 |
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Benign
(Dec 11, 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: SCV002372738.3
First in ClinVar: Apr 11, 2022 Last updated: Feb 14, 2024 |
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Likely benign
(Apr 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004127016.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
LDB3: BS1
Number of individuals with the variant: 3
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Likely benign
(Sep 03, 2020)
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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: SCV002708526.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925714.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953608.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965907.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002034882.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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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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Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. | van Lint FHM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30847666 |
Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy. | Lopes LR | Heart (British Cardiac Society) | 2015 | PMID: 25351510 |
Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy. | Golbus JR | Circulation. Cardiovascular genetics | 2014 | PMID: 25179549 |
Interpreting secondary cardiac disease variants in an exome cohort. | Ng D | Circulation. Cardiovascular genetics | 2013 | PMID: 23861362 |
A novel custom resequencing array for dilated cardiomyopathy. | Zimmerman RS | Genetics in medicine : official journal of the American College of Medical Genetics | 2010 | PMID: 20474083 |
Text-mined citations for rs372331627 ...
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.