ClinVar Genomic variation as it relates to human health
NM_000237.3(LPL):c.547G>A (p.Asp183Asn)
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_000237.3(LPL):c.547G>A (p.Asp183Asn)
Variation ID: 1066635 Accession: VCV001066635.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8p21.3 8: 19954125 (GRCh38) [ NCBI UCSC ] 8: 19811636 (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 10, 2021 Feb 14, 2024 Dec 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000237.3:c.547G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000228.1:p.Asp183Asn missense NC_000008.11:g.19954125G>A NC_000008.10:g.19811636G>A NG_008855.2:g.57409G>A LRG_1298:g.57409G>A LRG_1298t1:c.547G>A LRG_1298p1:p.Asp183Asn - Protein change
- D183N
- Other names
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- Canonical SPDI
- NC_000008.11:19954124: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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00002
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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LPL | - | - |
GRCh38 GRCh37 |
740 | 827 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Dec 14, 2023 | RCV001377679.5 | |
Likely pathogenic (2) |
criteria provided, single submitter
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Sep 15, 2021 | RCV001732177.3 | |
Pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV002246352.1 |
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
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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
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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
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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
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hyperlipoproteinemia, type I
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001983429.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
Comment:
Variant summary: LPL c.547G>A (p.Asp183Asn) results in a conservative amino acid change located in the Lipase/vitellogenin domain (IPR013818) of the encoded protein sequence. Four of … (more)
Variant summary: LPL c.547G>A (p.Asp183Asn) results in a conservative amino acid change located in the Lipase/vitellogenin domain (IPR013818) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 150872 control chromosomes (gnomAD v3.1, genomes dataset). The variant c.547G>A (aka. c.721G>A (p.Asp156Asn)) has been reported in the literature in a family in two compound heterozygous individuals who were affected with Familial Lipoprotein Lipase Deficiency (Ma_1992). These data indicate that the variant may be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated the complete loss of enzyme activity (Ma_1992, Emmerich_1992, Merkel_1998). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hyperlipidemia, familial combined, LPL related
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002517574.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Mar 24, 2021)
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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: SCV001983364.2
First in ClinVar: Oct 30, 2021 Last updated: Mar 04, 2023 |
Comment:
Not observed in large population cohorts (Lek et al., 2016); Published functional studies demonstrate a damaging effect on catalytic activity (Ma et al., 1992); In … (more)
Not observed in large population cohorts (Lek et al., 2016); Published functional studies demonstrate a damaging effect on catalytic activity (Ma et al., 1992); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 1730727, 1371284, 9811888, 11229871, 27055971, 15013626) (less)
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Likely pathogenic
(Dec 14, 2023)
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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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Invitae
Accession: SCV001575071.3
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 183 of the LPL protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 183 of the LPL protein (p.Asp183Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with chylomicronemia (PMID: 1730727). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Asp156Asn. ClinVar contains an entry for this variant (Variation ID: 1066635). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LPL protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects LPL function (PMID: 1730727). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Likely pathogenic
(Jun 09, 2020)
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no assertion criteria provided
Method: clinical testing
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Lipoprotein lipase deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002083207.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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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Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency. | Rodrigues R | Journal of clinical lipidology | 2016 | PMID: 27055971 |
Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: direct evidence that lipoprotein lipase bridging occurs in vivo. | Merkel M | Proceedings of the National Academy of Sciences of the United States of America | 1998 | PMID: 9811888 |
Two naturally occurring mutations at the first and second bases of codon aspartic acid 156 in the proposed catalytic triad of human lipoprotein lipase. In vivo evidence that aspartic acid 156 is essential for catalysis. | Ma YH | The Journal of biological chemistry | 1992 | PMID: 1730727 |
Human lipoprotein lipase. Analysis of the catalytic triad by site-directed mutagenesis of Ser-132, Asp-156, and His-241. | Emmerich J | The Journal of biological chemistry | 1992 | PMID: 1371284 |
Text-mined citations for rs781614031 ...
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.