Reported to be one of the most common LDLR variants in FH patients from the Netherlands (Defesche et al., 2008; Kusters et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Published functional studies demonstrate a damaging effect with abnormal gene splicing resulting in the in-frame deletion of 25 amino acids affecting the LDL-receptor class A5 domain (Defesche et al., 2008); Also known as G186=; This variant is associated with the following publications: (PMID: 22390909, 27821657, 18400033, 28104544, 32977124, 30293936, 33740630, 34037665, 21475731)
ClinVar Genomic variation as it relates to human health
NM_000527.5(LDLR):c.621C>T (p.Gly207=)
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.
(12)
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
12
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.621C>T (p.Gly207=)
Variation ID: 3747 Accession: VCV000003747.16
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 19p13.2 19: 11105527 (GRCh38) [ NCBI UCSC ] 19: 11216203 (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 Jul 29, 2016 May 1, 2024 Oct 6, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000527.5:c.621C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000518.1:p.Gly207= synonymous NM_001195798.2:c.621C>T NP_001182727.1:p.Gly207= synonymous NM_001195799.2:c.498C>T NP_001182728.1:p.Gly166= synonymous NM_001195800.2:c.314-1865C>T intron variant NM_001195803.2:c.314-1038C>T intron variant NC_000019.10:g.11105527C>T NC_000019.9:g.11216203C>T NG_009060.1:g.21147C>T LRG_274:g.21147C>T LRG_274t1:c.621C>T LRG_274p1:p.Gly207= - Protein change
- -
- Other names
-
G186G
NP_000518.1:p.Gly207Gly=
- Canonical SPDI
- NC_000019.10:11105526:C: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 |
4085 | 4361 | |
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 (9) |
criteria provided, multiple submitters, no conflicts
|
Sep 1, 2022 | RCV000003945.15 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 6, 2023 | RCV001389663.8 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 7, 2022 | RCV002254902.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 23, 2021 | RCV002362561.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely 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: SCV000748131.1
First in ClinVar: May 19, 2018 Last updated: May 19, 2018
Comment:
Variant present in the database from Uruguay
|
Observation 1: Observation 2:
Comment on evidence:
Assay Description:Htz patients lymphocytes, RNA assays
Result:
new splice site: deletion of 75 last nucleotides from exon 4 (p.Gly207_Cys231del)
|
|
|
Pathogenic
(Jun 07, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002526240.2
First in ClinVar: Jun 18, 2022 Last updated: Mar 04, 2023 |
Comment:
Reported to be one of the most common LDLR variants in FH patients from the Netherlands (Defesche et al., 2008; Kusters et al., 2011); Not … (more)
Reported to be one of the most common LDLR variants in FH patients from the Netherlands (Defesche et al., 2008; Kusters et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Published functional studies demonstrate a damaging effect with abnormal gene splicing resulting in the in-frame deletion of 25 amino acids affecting the LDL-receptor class A5 domain (Defesche et al., 2008); Also known as G186=; This variant is associated with the following publications: (PMID: 22390909, 27821657, 18400033, 28104544, 32977124, 30293936, 33740630, 34037665, 21475731) (less)
|
|
|
Pathogenic
(Sep 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175481.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
|
|
|
Pathogenic
(Oct 06, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Familial hypercholesterolemia
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001591108.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects codon 207 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid … (more)
This sequence change affects codon 207 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 25 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with familial hypercholesterolemia (PMID: 18400033, 28104544, 30293936). ClinVar contains an entry for this variant (Variation ID: 3747). Studies have shown that this variant results in the activation of a cryptic splice site in exon 4 (PMID: 18400033). This variant disrupts a region of the LDLR protein in which other variant(s) (p.Glu208Lys) have been determined to be pathogenic (PMID: 1301956, 18677035, 22390909). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
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: SCV000294826.2
First in ClinVar: Jul 29, 2016 Last updated: May 19, 2018 |
Number of individuals with the variant: 1
|
|
|
Likely 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: SCV000503190.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016 |
Comment:
subject mutated among 2600 FH index cases screened = 5, family member = 1
Number of individuals with the variant: 5
|
|
|
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: SCV000583711.1
First in ClinVar: Jul 29, 2016 Last updated: Jul 29, 2016
Comment:
ACMG Guidelines: Pathogenic (ii)
|
Number of individuals with the variant: 3
Clinical Features:
Hyperbetalipoproteinemia (present) , Hypercholesterolemia (present)
Indication for testing: Familial Hypercholesterolemia
Sex: mixed
Geographic origin: France
Comment on evidence:
Dutch Lipid Clinic Scoring : Probable FH
Secondary finding: no
|
|
|
Likely pathogenic
(Mar 01, 2016)
|
criteria provided, single submitter
Method: curation, literature only
|
Familial hypercholesterolemia
(Autosomal dominant inheritance)
Affected status: not applicable, unknown
Allele origin:
germline,
not applicable
|
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge
Accession: SCV000599336.1
First in ClinVar: Sep 09, 2017 Last updated: Sep 09, 2017 |
Observation 1: Observation 2:
Comment on evidence:
Assay Description:Htz patients lymphocytes, RNA assays
Result:
new splice site: deletion of 75 last nucleotides from exon 4 (p.Gly207_Cys231del)
|
|
|
Pathogenic
(Feb 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hypercholesterolemia, familial, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848336.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Gly207Gly variant in LDLR has been reported in >30 individuals with familial hypercholesterolemia (FH) and segregated with disease in numerous affected individuals from several … (more)
The p.Gly207Gly variant in LDLR has been reported in >30 individuals with familial hypercholesterolemia (FH) and segregated with disease in numerous affected individuals from several families; of note, at least 2 of these individuals were homozygous and displayed features of autosomal recessive FH (Defesche 2008 PMID: 18400033, Durst 2017 PMID: 28104544, Martín-Campos 2018 PMID: 30293936). This variant has been reported by other clinical laboratories in ClinVar (Variation ID 3747) and was absent from large population studies. Computational tools predict a splicing impact and an in vitro analyses supported an alteration of splicing leading to an in-frame deletion of 75 bp (Defesche 2008 PMID: 18400033, Martin-Campos 2018 PMID: 30293936). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant FH. ACMG/AMP criteria applied: PS4, PM2_Supporting, PP1_Strong, PS3_Supporting, PM3. (less)
|
|
|
Pathogenic
(Dec 23, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002659775.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.621C>T pathogenic mutation (also known as p.G207G), located in coding exon 4, results from a C to T substitution at nucleotide position 621 of … (more)
The c.621C>T pathogenic mutation (also known as p.G207G), located in coding exon 4, results from a C to T substitution at nucleotide position 621 of the LDLR gene. This nucleotide substitution does not change the amino acid at codon 207. This mutation has been reported in several familial hypercholesterolemia cohorts, and in one of the studies, the average LDL-C level in family members positive for the mutation was elevated compared with relatives who did not carry the alteration (Defesche JC et al. Clin. Genet. 2008;73:573-8; Kusters DM et al. Neth Heart J. 2011;19:175-182; Sánchez-Hernández RM et al. Circ Cardiovasc Genet. 2016;9:504-510; Durst R et al. Atherosclerosis. 2017;257:55-63). In addition, this mutation has been identified in the homozygous state in two unrelated individuals with LDL-C levels indicative of homozygous familial hypercholesterolemia, both of whom suffered myocardial infarction at a young age (Defesche JC et al. Clin. Genet. 2008;73:573-8). RNA studies indicate that the variant creates a cryptic donor splice site in coding exon 4 and results in the in-frame deletion of 25 amino acids in LDL type A repeat 5, which is important for ligand binding (Defesche JC et al. Clin. Genet. 2008;73:573-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
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: SCV000606170.1
First in ClinVar: Sep 30, 2017 Last updated: Sep 30, 2017 |
|
|
|
Pathogenic
(Jun 01, 2008)
|
no assertion criteria provided
Method: literature only
|
HYPERCHOLESTEROLEMIA, FAMILIAL, 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024110.3
First in ClinVar: Apr 04, 2013 Last updated: Jun 23, 2019 |
Comment on evidence:
In 35 unrelated Dutch patients clinically diagnosed with familial hypercholesterolemia who were negative for functional DNA variation in known hypercholesterolemia genes, Defesche et al. (2008) … (more)
In 35 unrelated Dutch patients clinically diagnosed with familial hypercholesterolemia who were negative for functional DNA variation in known hypercholesterolemia genes, Defesche et al. (2008) identified a 621C-T transition in exon 4 of the LDLR gene, resulting in a synonymous gly186-to-gly (G186G) change, that introduces a 3-prime splice donor site with a higher 'probability score' than the naturally occurring 3-prime splice site 75 bp downstream. Analysis of cDNA synthesized from total RNA revealed that the aberrant splicing results in a 75-bp in-frame deletion and a stable mRNA, predicted to produce an LDLR protein lacking a 25-amino acid fragment (gly186 to cys210). The variant was found in homozygosity in 2 of the probands, who had LDL cholesterol levels of 14.8 and 10.5 mmol/L, respectively, and who both suffered myocardial infarctions before the age of 20 years. The variant was also identified in 62 first-degree relatives of the index cases. (less)
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Comment:
Comment:
This sequence change affects codon 207 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 25 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with familial hypercholesterolemia (PMID: 18400033, 28104544, 30293936). ClinVar contains an entry for this variant (Variation ID: 3747). Studies have shown that this variant results in the activation of a cryptic splice site in exon 4 (PMID: 18400033). This variant disrupts a region of the LDLR protein in which other variant(s) (p.Glu208Lys) have been determined to be pathogenic (PMID: 1301956, 18677035, 22390909). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
subject mutated among 2600 FH index cases screened = 5, family member = 1
Comment:
The p.Gly207Gly variant in LDLR has been reported in >30 individuals with familial hypercholesterolemia (FH) and segregated with disease in numerous affected individuals from several families; of note, at least 2 of these individuals were homozygous and displayed features of autosomal recessive FH (Defesche 2008 PMID: 18400033, Durst 2017 PMID: 28104544, Martín-Campos 2018 PMID: 30293936). This variant has been reported by other clinical laboratories in ClinVar (Variation ID 3747) and was absent from large population studies. Computational tools predict a splicing impact and an in vitro analyses supported an alteration of splicing leading to an in-frame deletion of 75 bp (Defesche 2008 PMID: 18400033, Martin-Campos 2018 PMID: 30293936). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant FH. ACMG/AMP criteria applied: PS4, PM2_Supporting, PP1_Strong, PS3_Supporting, PM3.
Comment:
The c.621C>T pathogenic mutation (also known as p.G207G), located in coding exon 4, results from a C to T substitution at nucleotide position 621 of the LDLR gene. This nucleotide substitution does not change the amino acid at codon 207. This mutation has been reported in several familial hypercholesterolemia cohorts, and in one of the studies, the average LDL-C level in family members positive for the mutation was elevated compared with relatives who did not carry the alteration (Defesche JC et al. Clin. Genet. 2008;73:573-8; Kusters DM et al. Neth Heart J. 2011;19:175-182; Sánchez-Hernández RM et al. Circ Cardiovasc Genet. 2016;9:504-510; Durst R et al. Atherosclerosis. 2017;257:55-63). In addition, this mutation has been identified in the homozygous state in two unrelated individuals with LDL-C levels indicative of homozygous familial hypercholesterolemia, both of whom suffered myocardial infarction at a young age (Defesche JC et al. Clin. Genet. 2008;73:573-8). RNA studies indicate that the variant creates a cryptic donor splice site in coding exon 4 and results in the in-frame deletion of 25 amino acids in LDL type A repeat 5, which is important for ligand binding (Defesche JC et al. Clin. Genet. 2008;73:573-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
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:
Reported to be one of the most common LDLR variants in FH patients from the Netherlands (Defesche et al., 2008; Kusters et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Published functional studies demonstrate a damaging effect with abnormal gene splicing resulting in the in-frame deletion of 25 amino acids affecting the LDL-receptor class A5 domain (Defesche et al., 2008); Also known as G186=; This variant is associated with the following publications: (PMID: 22390909, 27821657, 18400033, 28104544, 32977124, 30293936, 33740630, 34037665, 21475731)
Comment:
This sequence change affects codon 207 of the LDLR mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LDLR protein. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 25 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with familial hypercholesterolemia (PMID: 18400033, 28104544, 30293936). ClinVar contains an entry for this variant (Variation ID: 3747). Studies have shown that this variant results in the activation of a cryptic splice site in exon 4 (PMID: 18400033). This variant disrupts a region of the LDLR protein in which other variant(s) (p.Glu208Lys) have been determined to be pathogenic (PMID: 1301956, 18677035, 22390909). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
subject mutated among 2600 FH index cases screened = 5, family member = 1
Comment:
The p.Gly207Gly variant in LDLR has been reported in >30 individuals with familial hypercholesterolemia (FH) and segregated with disease in numerous affected individuals from several families; of note, at least 2 of these individuals were homozygous and displayed features of autosomal recessive FH (Defesche 2008 PMID: 18400033, Durst 2017 PMID: 28104544, Martín-Campos 2018 PMID: 30293936). This variant has been reported by other clinical laboratories in ClinVar (Variation ID 3747) and was absent from large population studies. Computational tools predict a splicing impact and an in vitro analyses supported an alteration of splicing leading to an in-frame deletion of 75 bp (Defesche 2008 PMID: 18400033, Martin-Campos 2018 PMID: 30293936). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant FH. ACMG/AMP criteria applied: PS4, PM2_Supporting, PP1_Strong, PS3_Supporting, PM3.
Comment:
The c.621C>T pathogenic mutation (also known as p.G207G), located in coding exon 4, results from a C to T substitution at nucleotide position 621 of the LDLR gene. This nucleotide substitution does not change the amino acid at codon 207. This mutation has been reported in several familial hypercholesterolemia cohorts, and in one of the studies, the average LDL-C level in family members positive for the mutation was elevated compared with relatives who did not carry the alteration (Defesche JC et al. Clin. Genet. 2008;73:573-8; Kusters DM et al. Neth Heart J. 2011;19:175-182; Sánchez-Hernández RM et al. Circ Cardiovasc Genet. 2016;9:504-510; Durst R et al. Atherosclerosis. 2017;257:55-63). In addition, this mutation has been identified in the homozygous state in two unrelated individuals with LDL-C levels indicative of homozygous familial hypercholesterolemia, both of whom suffered myocardial infarction at a young age (Defesche JC et al. Clin. Genet. 2008;73:573-8). RNA studies indicate that the variant creates a cryptic donor splice site in coding exon 4 and results in the in-frame deletion of 25 amino acids in LDL type A repeat 5, which is important for ligand binding (Defesche JC et al. Clin. Genet. 2008;73:573-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. | Sturm AC | JAMA cardiology | 2021 | PMID: 34037665 |
| Molecular genetic testing for autosomal dominant hypercholesterolemia in 29,449 Norwegian index patients and 14,230 relatives during the years 1993-2020. | Leren TP | Atherosclerosis | 2021 | PMID: 33740630 |
| Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features. | Bertolini S | Atherosclerosis | 2020 | PMID: 32977124 |
| Autosomal dominant hypercholesterolemia in Catalonia: Correspondence between clinical-biochemical and genetic diagnostics in 967 patients studied in a multicenter clinical setting. | Martín-Campos JM | Journal of clinical lipidology | 2018 | PMID: 30293936 |
| Molecular genetics of familial hypercholesterolemia in Israel-revisited. | Durst R | Atherosclerosis | 2017 | PMID: 28104544 |
| Homozygous Familial Hypercholesterolemia in Spain: Prevalence and Phenotype-Genotype Relationship. | Sánchez-Hernández RM | Circulation. Cardiovascular genetics | 2016 | PMID: 27784735 |
| Current novel-gene-finding strategy for autosomal-dominant hypercholesterolaemia needs refinement. | Fouchier SW | Journal of medical genetics | 2015 | PMID: 25412742 |
| Cardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29,365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variants. | Huijgen R | European heart journal | 2012 | PMID: 22390909 |
| Founder mutations in the Netherlands: geographical distribution of the most prevalent mutations in the low-density lipoprotein receptor and apolipoprotein B genes. | Kusters DM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2011 | PMID: 21475731 |
| Molecular basis of autosomal dominant hypercholesterolemia: assessment in a large cohort of hypercholesterolemic children. | van der Graaf A | Circulation | 2011 | PMID: 21382890 |
| The epidermal growth factor homology domain of the LDL receptor drives lipoprotein release through an allosteric mechanism involving H190, H562, and H586. | Zhao Z | The Journal of biological chemistry | 2008 | PMID: 18677035 |
| Silent exonic mutations in the low-density lipoprotein receptor gene that cause familial hypercholesterolemia by affecting mRNA splicing. | Defesche JC | Clinical genetics | 2008 | PMID: 18400033 |
| Molecular genetics of the LDL receptor gene in familial hypercholesterolemia. | Hobbs HH | Human mutation | 1992 | PMID: 1301956 |
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Text-mined citations for rs121908044 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.