NM_000527.5(LDLR):c.313+5G>A AND Familial hypercholesterolemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 12, 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:: RCV002519838.3

Allele description [Variation Report for NM_000527.5(LDLR):c.313+5G>A]

NM_000527.5(LDLR):c.313+5G>A

Gene:

LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.313+5G>A

HGVS:

NC_000019.10:g.11102791G>A
NG_009060.1:g.18411G>A
NM_000527.5:c.313+5G>AMANE SELECT
NM_001195798.2:c.313+5G>A
NM_001195799.2:c.191-2429G>A
NM_001195800.2:c.313+5G>A
NM_001195803.2:c.313+5G>A
LRG_274t1:c.313+5G>A
LRG_274:g.18411G>A
NC_000019.9:g.11213467G>A
NM_000527.4:c.313+5G>A
c.313+5G>A

Links:

LDLR-LOVD, British Heart Foundation: LDLR_001017;

Molecular consequence:

NM_000527.5:c.313+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195798.2:c.313+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195799.2:c.191-2429G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195800.2:c.313+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.313+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

Recent activity

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HPODL_03743 [Ogataea parapolymorpha DL-1]
HPODL_03743 [Ogataea parapolymorpha DL-1]
Gene ID:25773177

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443095	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11317362, 17094996, 30592178, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443095

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

LDL receptor cDNA sequence analysis in familial hypercholesterolemia patients: 5 novel mutations with high prevalence in families originating from southern Italy.

Liguori R, Bianco AM, Argiriou A, Pauciullo P, Giannino A, Rubba P, De Simone V.

Hum Mutat. 2001 May;17(5):433.

PubMed [citation]

PMID:: 11317362

Genetic defects causing familial hypercholesterolaemia: identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic.

Tosi I, Toledo-Leiva P, Neuwirth C, Naoumova RP, Soutar AK.

Atherosclerosis. 2007 Sep;194(1):102-11. Epub 2006 Nov 13.

PubMed [citation]

PMID:: 17094996

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443095.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change falls in intron 3 of the LDLR gene. It does not directly change the encoded amino acid sequence of the LDLR protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of familial hypercholesterolemia (PMID: 11317362, 17094996, 30592178; Invitae). ClinVar contains an entry for this variant (Variation ID: 251136). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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