ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.91G>T (p.Glu31Ter)
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_000527.5(LDLR):c.91G>T (p.Glu31Ter)
Variation ID: 251014 Accession: VCV000251014.4
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.2 19: 11100246 (GRCh38) [ NCBI UCSC ] 19: 11210922 (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 Jul 29, 2016 Nov 29, 2022 Jun 21, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000527.5:c.91G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Glu31Ter nonsense NM_001195798.2:c.91G>T NP_001182727.1:p.Glu31Ter nonsense NM_001195799.2:c.91G>T NP_001182728.1:p.Glu31Ter nonsense NM_001195800.2:c.91G>T NP_001182729.1:p.Glu31Ter nonsense NM_001195803.2:c.91G>T NP_001182732.1:p.Glu31Ter nonsense NC_000019.10:g.11100246G>T NC_000019.9:g.11210922G>T NG_009060.1:g.15866G>T LRG_274:g.15866G>T LRG_274t1:c.91G>T LRG_274p1:p.Glu31Ter - Protein change
- E31*
- Other names
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- Canonical SPDI
- NC_000019.10:11100245:G:T
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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.
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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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LDLR | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3895 | 4139 |
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
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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 (5) |
criteria provided, multiple submitters, no conflicts
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Mar 30, 2017 | RCV000238408.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 21, 2021 | RCV001532988.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 28, 2018 | RCV002446470.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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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Pathogenic
(Mar 25, 2016)
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criteria provided, single submitter
Method: literature only
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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LDLR-LOVD, British Heart Foundation
Accession: SCV000294460.2
First in ClinVar: Jul 29, 2016 Last updated: Sep 30, 2017 |
Observation 1:
Number of individuals with the variant: 1
Observation 2:
Number of individuals with the variant: 1
Observation 3:
Number of individuals with the variant: 1
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Pathogenic
(Dec 16, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
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Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503100.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
subjects mutated among 2600 FH index cases screened = 3 , family member = 1 with co-segregation
Number of individuals with the variant: 3
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Pathogenic
(Mar 30, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial Hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille
Accession: SCV000583629.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
ACMG Guidelines: Pathogenic (ii)
Number of individuals with the variant: 1
Clinical Features:
Hyperbetalipoproteinemia (present) , Hypercholesterolemia (present)
Indication for testing: Familial Hypercholesterolemia
Geographic origin: France
Comment on evidence:
Dutch Lipid Clinic Scoring : Definite FH
Secondary finding: no
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Pathogenic
(Mar 01, 2016)
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criteria provided, single submitter
Method: research
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Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Fundacion Hipercolesterolemia Familiar
Study: SAFEHEART
Accession: SCV000607414.1 First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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Pathogenic
(Jun 21, 2021)
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criteria provided, single submitter
Method: clinical testing
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001748821.1
First in ClinVar: Jul 10, 2021 Last updated: Jul 10, 2021 |
Comment:
Variant summary: LDLR c.91G>T (p.Glu31X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: LDLR c.91G>T (p.Glu31X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251034 control chromosomes (gnomAD). c.91G>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia. Several of these patients were of Spanish origin and in many families the variant co-segregated with high cholesterol concentrations (example: Cenarro_1996, Wintjens_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jan 28, 2018)
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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: SCV002682234.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.E31* pathogenic mutation (also known as c.91G>T), located in coding exon 2 of the LDLR gene, results from a G to T substitution at … (more)
The p.E31* pathogenic mutation (also known as c.91G>T), located in coding exon 2 of the LDLR gene, results from a G to T substitution at nucleotide position 91. This changes the amino acid from a glutamic acid to a stop codon within coding exon 2. This mutation (historically described as p.E10*) has been reported in multiple individuals with familial hypercholesterolemia (FH) from a variety of ancestries (Cenarro A et al. Clin. Genet., 1996 Apr;49:180-5; Reshef A et al. Hum. Genet., 1996 Nov;98:581-6; Descamps OS et al. Eur. J. Clin. Invest., 2001 Nov;31:958-65). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Number of individuals with the variant: 1
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
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Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
Accession: SCV000606013.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
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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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Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France. | Wintjens R | Journal of lipid research | 2016 | PMID: 26802169 |
Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia. | Descamps OS | European journal of clinical investigation | 2001 | PMID: 11737238 |
Molecular genetics of familial hypercholesterolemia in Israel. | Reshef A | Human genetics | 1996 | PMID: 8882879 |
Two novel mutations in the LDL receptor gene: common causes of familial hypercholesterolemia in a Spanish population. | Cenarro A | Clinical genetics | 1996 | PMID: 8828982 |
Text-mined citations for rs776421777 ...
HelpRecord last updated Aug 06, 2023
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.