subjects mutated among 2600 FH index cases screened = 11 , family members = 8 with co-segregation
ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.337G>T (p.Glu113Ter)
Germline
Classification
Help
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.
(15)
Help
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.
Pathogenic/Likely pathogenic
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000527.5(LDLR):c.337G>T (p.Glu113Ter)
Variation ID: 226320 Accession: VCV000226320.18
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19p13.2 19: 11105243 (GRCh38) [ NCBI UCSC ] 19: 11215919 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 22, 2016 Sep 16, 2024 Jan 5, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000527.5:c.337G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Glu113Ter nonsense NM_001195798.2:c.337G>T NP_001182727.1:p.Glu113Ter nonsense NM_001195799.2:c.214G>T NP_001182728.1:p.Glu72Ter nonsense NM_001195800.2:c.314-2149G>T intron variant NM_001195803.2:c.314-1322G>T intron variant NC_000019.10:g.11105243G>T NC_000019.9:g.11215919G>T NG_009060.1:g.20863G>T LRG_274:g.20863G>T LRG_274t1:c.337G>T LRG_274p1:p.Glu113Ter - Protein change
- E113*, E72*
- Other names
-
FH Paris-5
NP_000518.1:p.E113*
- Canonical SPDI
- NC_000019.10:11105242:G:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 | ||
|---|---|---|---|---|---|---|
| HI score
Help
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. |
|||
| LDLR | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
4076 | 4352 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (11) |
criteria provided, multiple submitters, no conflicts
|
May 24, 2021 | RCV000211560.16 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 5, 2024 | RCV000523979.4 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 13, 2023 | RCV002229195.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 11, 2022 | RCV002453756.2 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Mar 25, 2016)
|
criteria provided, single submitter
Method: literature only
|
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
LDLR-LOVD, British Heart Foundation
Accession: SCV000294637.2
First in ClinVar: Jul 29, 2016 Last updated: Oct 10, 2018 |
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
Observation 4:
Number of individuals with the variant: 1
Observation 5:
Number of individuals with the variant: 1
|
|
|
Likely pathogenic
(-)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Robarts Research Institute, Western University
Accession: SCV000484731.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Number of individuals with the variant: 2
|
|
|
Pathogenic
(Dec 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
|
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix
Accession: SCV000503142.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
subjects mutated among 2600 FH index cases screened = 11 , family members = 8 with co-segregation
Number of individuals with the variant: 11
|
|
|
Pathogenic
(Mar 30, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial Hypercholesterolemia
Affected status: yes
Allele origin:
germline
|
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille
Accession: SCV000583663.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016
Comment:
ACMG Guidelines: Pathogenic (ii)
|
Number of individuals with the variant: 19
Clinical Features:
Hyperbetalipoproteinemia (present) , Hypercholesterolemia (present)
Indication for testing: Familial Hypercholesterolemia
Sex: mixed
Geographic origin: France
Comment on evidence:
Dutch Lipid Clinic Scoring : Definite FH
Secondary finding: no
|
|
|
Pathogenic
(Mar 01, 2016)
|
criteria provided, single submitter
Method: research
|
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory of Genetics and Molecular Cardiology, University of São Paulo
Study: HipercolBrasil
Accession: SCV000588497.1 First in ClinVar: Aug 13, 2017 Last updated: Aug 13, 2017 |
Observation 1: Observation 2:
Comment on evidence:
Assay description:Comp Htz (with p.(Glu228Lys)) patients' fibroblasts, 125I-LDL assays
Result:
<2% LDLR activity
|
|
|
Pathogenic
(Mar 01, 2016)
|
criteria provided, single submitter
Method: research
|
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Iberoamerican FH Network
Accession: SCV000748084.1
First in ClinVar: May 19, 2018 Last updated: May 19, 2018
Comment:
Variant present in the database from Argentina
|
Observation 1: Observation 2:
Comment on evidence:
Assay Description:Comp Htz (with p.(Glu228Lys)) patients' fibroblasts, 125I-LDL assays
Result:
<2% LDLR activity
|
|
|
Pathogenic
(May 11, 2019)
|
criteria provided, single submitter
Method: research
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
|
Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia
Accession: SCV001432646.1
First in ClinVar: Sep 19, 2020 Last updated: Sep 19, 2020 |
Number of individuals with the variant: 1
Clinical Features:
Dutch Lipid Clinic Network Criteria score (present) , low-density lipoprotein cholesterol level (present)
|
|
|
Pathogenic
(May 24, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
|
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II
Accession: SCV001653587.1
First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021 |
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
|
|
|
Pathogenic
(May 06, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002769519.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypercholesterolemia 1 and LDL cholesterol level QTL2 (MIM#143890). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (GeneReviews). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in many patients with familial hypercholesterolemia (ClinVar), both heterozygous (PMID:28502510) and homozygous (PMID:26894473). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
|
|
|
Pathogenic
(Oct 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000833264.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu113*) in the LDLR gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu113*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 10532689, 11196104, 11462246, 11933210). This variant is also known as Stop 92, E92X. ClinVar contains an entry for this variant (Variation ID: 226320). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(May 11, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002614438.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.E113* pathogenic mutation (also known as c.337G>T), located in coding exon 4 of the LDLR gene, results from a G to T substitution at … (more)
The p.E113* pathogenic mutation (also known as c.337G>T), located in coding exon 4 of the LDLR gene, results from a G to T substitution at nucleotide position 337. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This alteration, also known as p.E92*, has been reported in patients with familial hypercholesterolemia (FH) (Hobbs HH et al. Hum. Mutat., 1992;1:445-66; Jensen HK et al. Atherosclerosis, 1999 Oct;146:337-44; Szalai C et al. Clin. Genet., 1999 Jan;55:67-8; Weiss N et al. J. Inherit. Metab. Dis., 2000 Dec;23:778-90; Salazar LA et al. Hum. Mutat., 2002 Apr;19:462-3). This alteration has also been reported in a homozygous state in a pediatric FH cohort (Sanna C et al. Atherosclerosis, 2016 Apr;247:97-104). 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)
|
|
|
Pathogenic
(Jan 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000617502.3
First in ClinVar: Dec 19, 2017 Last updated: Sep 16, 2024 |
Comment:
Has been reported in multiple unrelated individuals with FH (PMID: 28502510, 1301956, 27765764, 32041611, 33303402, 34037665, 34297352, 31345425, 11933210, 35052492, 11462246, 11196104); Not observed at … (more)
Has been reported in multiple unrelated individuals with FH (PMID: 28502510, 1301956, 27765764, 32041611, 33303402, 34037665, 34297352, 31345425, 11933210, 35052492, 11462246, 11196104); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Also known as E92X and FH Paris-5; This variant is associated with the following publications: (PMID: 25525159, 1301956, 32041611, 28502510, 33303402, 34297352, 33955087, 26894473, 27765764, 34037665, 31345425, 11933210, 35052492, 11462246, 11196104, 10532689, 10066037, 37128917) (less)
|
|
|
Pathogenic
(Jul 13, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005198644.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
|
Pathogenic
(May 28, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: yes
Allele origin:
germline
|
Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital
Accession: SCV000268558.1
First in ClinVar: May 22, 2016 Last updated: May 22, 2016 |
Number of individuals with the variant: 4
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: research
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum
Accession: SCV000606090.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
|
|
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Comment:
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypercholesterolemia 1 and LDL cholesterol level QTL2 (MIM#143890). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (GeneReviews). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in many patients with familial hypercholesterolemia (ClinVar), both heterozygous (PMID:28502510) and homozygous (PMID:26894473). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
This sequence change creates a premature translational stop signal (p.Glu113*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 10532689, 11196104, 11462246, 11933210). This variant is also known as Stop 92, E92X. ClinVar contains an entry for this variant (Variation ID: 226320). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.E113* pathogenic mutation (also known as c.337G>T), located in coding exon 4 of the LDLR gene, results from a G to T substitution at nucleotide position 337. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This alteration, also known as p.E92*, has been reported in patients with familial hypercholesterolemia (FH) (Hobbs HH et al. Hum. Mutat., 1992;1:445-66; Jensen HK et al. Atherosclerosis, 1999 Oct;146:337-44; Szalai C et al. Clin. Genet., 1999 Jan;55:67-8; Weiss N et al. J. Inherit. Metab. Dis., 2000 Dec;23:778-90; Salazar LA et al. Hum. Mutat., 2002 Apr;19:462-3). This alteration has also been reported in a homozygous state in a pediatric FH cohort (Sanna C et al. Atherosclerosis, 2016 Apr;247:97-104). 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.
Comment:
Has been reported in multiple unrelated individuals with FH (PMID: 28502510, 1301956, 27765764, 32041611, 33303402, 34037665, 34297352, 31345425, 11933210, 35052492, 11462246, 11196104); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Also known as E92X and FH Paris-5; This variant is associated with the following publications: (PMID: 25525159, 1301956, 32041611, 28502510, 33303402, 34297352, 33955087, 26894473, 27765764, 34037665, 31345425, 11933210, 35052492, 11462246, 11196104, 10532689, 10066037, 37128917)
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. |
Comment:
subjects mutated among 2600 FH index cases screened = 11 , family members = 8 with co-segregation
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypercholesterolemia 1 and LDL cholesterol level QTL2 (MIM#143890). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance (GeneReviews). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v2) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, DECIPHER). (SP) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in many patients with familial hypercholesterolemia (ClinVar), both heterozygous (PMID:28502510) and homozygous (PMID:26894473). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Comment:
This sequence change creates a premature translational stop signal (p.Glu113*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 10532689, 11196104, 11462246, 11933210). This variant is also known as Stop 92, E92X. ClinVar contains an entry for this variant (Variation ID: 226320). For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.E113* pathogenic mutation (also known as c.337G>T), located in coding exon 4 of the LDLR gene, results from a G to T substitution at nucleotide position 337. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. This alteration, also known as p.E92*, has been reported in patients with familial hypercholesterolemia (FH) (Hobbs HH et al. Hum. Mutat., 1992;1:445-66; Jensen HK et al. Atherosclerosis, 1999 Oct;146:337-44; Szalai C et al. Clin. Genet., 1999 Jan;55:67-8; Weiss N et al. J. Inherit. Metab. Dis., 2000 Dec;23:778-90; Salazar LA et al. Hum. Mutat., 2002 Apr;19:462-3). This alteration has also been reported in a homozygous state in a pediatric FH cohort (Sanna C et al. Atherosclerosis, 2016 Apr;247:97-104). 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.
Comment:
Has been reported in multiple unrelated individuals with FH (PMID: 28502510, 1301956, 27765764, 32041611, 33303402, 34037665, 34297352, 31345425, 11933210, 35052492, 11462246, 11196104); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Also known as E92X and FH Paris-5; This variant is associated with the following publications: (PMID: 25525159, 1301956, 32041611, 28502510, 33303402, 34297352, 33955087, 26894473, 27765764, 34037665, 31345425, 11933210, 35052492, 11462246, 11196104, 10532689, 10066037, 37128917)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Analysis of LDLR variants from homozygous FH patients carrying multiple mutations in the LDLR gene. | Jiang L | Atherosclerosis | 2017 | PMID: 28645073 |
| Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina. | Bañares VG | Journal of clinical lipidology | 2017 | PMID: 28502510 |
| Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives. | Sanna C | Atherosclerosis | 2016 | PMID: 26894473 |
| RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
| Molecular spectrum of autosomal dominant hypercholesterolemia in France. | Marduel M | Human mutation | 2010 | PMID: 20809525 |
| Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations. | Salazar LA | Human mutation | 2002 | PMID: 11933210 |
| Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia. | Nauck MS | Human mutation | 2001 | PMID: 11462246 |
| Mutations in the low-density-lipoprotein receptor gene in German patients with familial hypercholesterolaemia. | Weiss N | Journal of inherited metabolic disease | 2000 | PMID: 11196104 |
| Spectrum of LDL receptor gene mutations in Denmark: implications for molecular diagnostic strategy in heterozygous familial hypercholesterolemia. | Jensen HK | Atherosclerosis | 1999 | PMID: 10532689 |
| Genetic investigation of patients with hypercholesterolemia type IIa. | Szalai C | Clinical genetics | 1999 | PMID: 10066037 |
| Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. | Hobbs HH | Human mutation | 1992 | PMID: 1301956 |
| Local prostaglandin E2 in patients with oral malignancies undergoing chemo- and radiotherapy. | Porteder H | Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery | 1988 | PMID: 3204161 |
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Text-mined citations for this variant ...
HelpRecord last updated Sep 29, 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.