NM_000527.5(LDLR):c.1120_1123dup (p.Tyr375fs) AND Hypercholesterolemia, familial, 1

Germline classification:: 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:: RCV000237857.3

Allele description [Variation Report for NM_000527.5(LDLR):c.1120_1123dup (p.Tyr375fs)]

NM_000527.5(LDLR):c.1120_1123dup (p.Tyr375fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.1120_1123dup (p.Tyr375fs)

Other names:

FH Pisa

HGVS:

NC_000019.10:g.11111573_11111576dup
NG_009060.1:g.27193_27196dup
NM_000527.5:c.1120_1123dupMANE SELECT
NM_001195798.2:c.1120_1123dup
NM_001195799.2:c.997_1000dup
NM_001195800.2:c.616_619dup
NM_001195803.2:c.739_742dup
NP_000518.1:p.Tyr375fs
NP_000518.1:p.Tyr375fs
NP_001182727.1:p.Tyr375fs
NP_001182728.1:p.Tyr334fs
NP_001182729.1:p.Tyr207fs
NP_001182732.1:p.Tyr248fs
LRG_274t1:c.1120_1123dup
LRG_274:g.27193_27196dup
LRG_274p1:p.Tyr375fs
NC_000019.9:g.11222247_11222248insTGGC
NC_000019.9:g.11222249_11222252dup
NM_000527.4:c.1120_1123dup
NM_000527.4:c.1120_1123dupGGCT
c.1120_1123dup
p.(Tyr375Trpfs*7)
p.Tyr375Trpfs*7

Protein change:

Y207fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000527; dbSNP: rs879254799

NCBI 1000 Genomes Browser:

rs879254799

Molecular consequence:

NM_000527.5:c.1120_1123dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.1120_1123dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.997_1000dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.616_619dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.739_742dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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Protein
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gi|514254580|gb|KC404517.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000295232	LDLR-LOVD, British Heart Foundation	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 25, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10660340, 23375686 Citation Link,
SCV000503301	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]
SCV001653622	Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10660340, 30710474, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000295232

LDLR-LOVD, British Heart Foundation

criteria provided, single submitter

(ACGS Guidelines, 2013)

Pathogenic
(Mar 25, 2016)

germline

literature only

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

Citation Link,

SCV000503301

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]

SCV001653622

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 24, 2021)

germline

clinical testing

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

Citations

PubMed

Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy.

Bertolini S, Pisciotta L, Rabacchi C, Cefalù AB, Noto D, Fasano T, Signori A, Fresa R, Averna M, Calandra S.

Atherosclerosis. 2013 Apr;227(2):342-8. doi: 10.1016/j.atherosclerosis.2013.01.007. Epub 2013 Jan 19.

PubMed [citation]

PMID:: 23375686

Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online.

Motti C, Bertolini S, Rampa P, Trovatello G, Liberatoscioli L, Calandra S, Federici G, Cortese C.

Hum Mutat. 1998;12(3):290.

PubMed [citation]

PMID:: 10660340

See all PubMed Citations (4)

Details of each submission

From LDLR-LOVD, British Heart Foundation, SCV000295232.2

#	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, SCV000503301.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

Description

subjects mutated among 2600 FH index cases screened = 3 / 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		3	not provided	not provided	not provided

From Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II, SCV001653622.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	2	not provided	not provided	clinical testing	PubMed (3)

#	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		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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