ClinVar Genomic variation as it relates to human health
NM_007078.3(LDB3):c.1153A>G (p.Ser385Gly)
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.1153A>G (p.Ser385Gly)
Variation ID: 228793 Accession: VCV000228793.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.2 10: 86709972 (GRCh38) [ NCBI UCSC ] 10: 88469729 (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 29, 2016 Feb 20, 2024 Jul 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007078.3:c.1153A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009009.1:p.Ser385Gly missense NM_001080114.2:c.823A>G NP_001073583.1:p.Ser275Gly missense NM_001171610.2:c.1168A>G NP_001165081.1:p.Ser390Gly missense NM_001368064.1:c.964A>G NP_001354993.1:p.Ser322Gly missense NM_001368065.1:c.964A>G NP_001354994.1:p.Ser322Gly missense NM_001368066.1:c.1012A>G NP_001354995.1:p.Ser338Gly missense NC_000010.11:g.86709972A>G NC_000010.10:g.88469729A>G NG_008876.1:g.46409A>G LRG_385:g.46409A>G LRG_385t1:c.1153A>G - Protein change
- S385G, S338G, S275G, S322G, S390G
- Other names
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- Canonical SPDI
- NC_000010.11:86709971: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
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00002
Trans-Omics for Precision Medicine (TOPMed) 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
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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
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
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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Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Jun 6, 2023 | RCV000219802.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 26, 2023 | RCV001247702.7 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 31, 2022 | RCV002347843.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 23, 2021 | RCV002478769.1 |
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
(Mar 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Accession: SCV000740597.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
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Uncertain significance
(Oct 01, 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: SCV000271908.2
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
Comment:
Variant classified as Uncertain Significance - Favor Benign. The p.Ser385Gly var iant in LDB3 has not been previously reported in individuals with cardiomyopathy , but … (more)
Variant classified as Uncertain Significance - Favor Benign. The p.Ser385Gly var iant in LDB3 has not been previously reported in individuals with cardiomyopathy , but has been identified in 1/63978 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org). Serine (Ser) at position 3 85 is not conserved in mammals or evolutionarily distant species and 9 species, including 3 mammals (Elephant, Elephant Shrew, Cape Golden Mole) carry a glycine (Gly) at this position, raising the possibility that this change may be tolerat ed. In summary, while the clinical significance of the p.Ser385Gly variant is un certain, these data suggest that it is more likely to be benign. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Mar 31, 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: SCV002622177.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.S385G variant (also known as c.1153A>G), located in coding exon 8 of the LDB3 gene, results from an A to G substitution at nucleotide … (more)
The p.S385G variant (also known as c.1153A>G), located in coding exon 8 of the LDB3 gene, results from an A to G substitution at nucleotide position 1153. The serine at codon 385 is replaced by glycine, an amino acid with 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
(Jul 23, 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: SCV002787342.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Jun 06, 2023)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004021066.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: LDB3 c.1153A>G (p.Ser385Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Variant summary: LDB3 c.1153A>G (p.Ser385Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248778 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1153A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Jul 26, 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: SCV001421140.5
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 output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs777547764, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 385 of the LDB3 protein (p.Ser385Gly). The LDB3 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_007078.3, and corresponds to NM_001080116.1:c.*10598A>G in the primary transcript. (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 rs777547764 ...
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.