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NC_000019.10:g.11089413C>T AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 2, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001854881.14

Allele description [Variation Report for NC_000019.10:g.11089413C>T]

NC_000019.10:g.11089413C>T

Genes:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
LDLR-AS1:LDLR antisense RNA 1 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NC_000019.10:g.11089413C>T
HGVS:
  • NC_000019.10:g.11089413C>T
  • NG_009060.1:g.5033C>T
  • NM_000527.4:c.-136C>T
  • NM_001195798.1:c.-136C>T
  • NM_001195799.1:c.-136C>T
  • NM_001195800.1:c.-136C>T
  • NM_001195803.1:c.-136C>T
  • LRG_274t1:c.-136C>T
  • LRG_274:g.5033C>T
  • NC_000019.9:g.11200089C>T
  • NR_163945.1:n.247G>A
  • c.-136C>T
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001261; dbSNP: rs879254374
NCBI 1000 Genomes Browser:
rs879254374
Molecular consequence:
  • NR_163945.1:n.247G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial hypercholesterolemia
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

Recent activity

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  • RecName: Full=AP-1 complex subunit mu-2; AltName: Full=AP-mu chain family member...
    RecName: Full=AP-1 complex subunit mu-2; AltName: Full=AP-mu chain family member mu1B; AltName: Full=Adaptor protein complex AP-1 subunit mu-2; AltName: Full=Adaptor-related protein complex 1 subunit mu-2; AltName: Full=Clathrin assembly protein complex 1 mu-2 medium chain 2; AltName: Full=Golgi adaptor HA1/AP1 adaptin mu-2 subunit; AltName: Full=Mu-adaptin 2; AltName: Full=Mu1B-adaptin
    gi|13123953|sp|Q9Y6Q5.4|AP1M2_HUMAN
    Protein

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002238412Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 2, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A single-base substitution in the proximal Sp1 site of the human low density lipoprotein receptor promoter as a cause of heterozygous familial hypercholesterolemia.

Koivisto UM, Palvimo JJ, Jänne OA, Kontula K.

Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10526-30.

PubMed [citation]
PMID:
7937987
PMCID:
PMC45054

An LDL receptor promoter mutation in a heterozygous FH patient with dramatically skewed ratio between the two allelic mRNA variants.

Jensen LG, Jensen HK, Nissen H, Kristiansen K, Faergeman O, Bolund L, Gregersen N.

Hum Mutat. 1996;7(1):82-4. No abstract available.

PubMed [citation]
PMID:
8664911
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238412.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant alters LDLR gene expression (PMID: 7937987). ClinVar contains an entry for this variant (Variation ID: 250955). This variant is also known as C-to-T substitution at position -43. This variant has been observed in individuals with familial hypercholesterolemia (PMID: 7937987, 8664911, 15199436, 15359125, 16250003). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024