NM_000527.5(LDLR):c.1698_1704delinsGCCCAAT (p.Ile566_Leu568delinsMetProAsn) AND Hypercholesterolemia, familial, 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 24, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000238027.4

Allele description [Variation Report for NM_000527.5(LDLR):c.1698_1704delinsGCCCAAT (p.Ile566_Leu568delinsMetProAsn)]

NM_000527.5(LDLR):c.1698_1704delinsGCCCAAT (p.Ile566_Leu568delinsMetProAsn)

Gene:

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

Variant type:

Indel

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1698_1704delinsGCCCAAT (p.Ile566_Leu568delinsMetProAsn)

HGVS:

NC_000019.10:g.11116205_11116211delinsGCCCAAT
NG_009060.1:g.31825_31831delinsGCCCAAT
NM_000527.5:c.1698_1704delinsGCCCAATMANE SELECT
NM_001195798.2:c.1698_1704delinsGCCCAAT
NM_001195799.2:c.1575_1581delinsGCCCAAT
NM_001195800.2:c.1194_1200delinsGCCCAAT
NM_001195803.2:c.1317_1323delinsGCCCAAT
NP_000518.1:p.Ile566_Leu568delinsMetProAsn
NP_001182727.1:p.Ile566_Leu568delinsMetProAsn
NP_001182728.1:p.Ile525_Leu527delinsMetProAsn
NP_001182729.1:p.Ile398_Leu400delinsMetProAsn
NP_001182732.1:p.Ile439_Leu441delinsMetProAsn
LRG_274:g.31825_31831delinsGCCCAAT
NC_000019.9:g.11226881_11226887delinsGCCCAAT
c.1698_1704delinsGCCCAAT
p.(Ile566_Leu568delinsMetProAsn)

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000365; dbSNP: rs879254989

NCBI 1000 Genomes Browser:

rs879254989

Molecular consequence:

NM_000527.5:c.1698_1704delinsGCCCAAT - missense variant - [Sequence Ontology: SO:0001583]
NM_001195798.2:c.1698_1704delinsGCCCAAT - missense variant - [Sequence Ontology: SO:0001583]
NM_001195799.2:c.1575_1581delinsGCCCAAT - missense variant - [Sequence Ontology: SO:0001583]
NM_001195800.2:c.1194_1200delinsGCCCAAT - missense variant - [Sequence Ontology: SO:0001583]
NM_001195803.2:c.1317_1323delinsGCCCAAT - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypercholesterolemia, familial, 1
Synonyms:: LDL RECEPTOR DISORDER; Hyperlipoproteinemia Type IIa; HYPER-LOW-DENSITY-LIPOPROTEINEMIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007750; MedGen: C0745103; Orphanet: 391665; OMIM: 143890

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295585	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Likely pathogenic (Mar 25, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11317362, 11600564 Citation Link,
SCV000503389	Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 16, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001653647	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11317362, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295585

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Likely pathogenic
(Mar 25, 2016)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000503389

Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 16, 2016)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001653647

Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 24, 2021)

germline

clinical testing

PubMed (2)
[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	yes	3	not provided	not provided	2602	not provided	clinical testing, literature only
Caucasian	germline	yes	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

Chaves FJ, Real JT, García-García AB, Civera M, Armengod ME, Ascaso JF, Carmena R.

J Clin Endocrinol Metab. 2001 Oct;86(10):4926-32.

PubMed [citation]

PMID:: 11600564

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

See all PubMed Citations (3)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295585.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	literature only	PubMed (2)
2	not provided	1	not provided	not provided	literature only	PubMed (2)

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

From Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix, SCV000503389.1

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

Description

subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	2600	not provided	not provided		1	not provided	not provided	not provided

From Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653647.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	4	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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