NM_000527.5(LDLR):c.2416dup (p.Val806fs) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 30, 2022
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:: RCV000486216.9

Allele description [Variation Report for NM_000527.5(LDLR):c.2416dup (p.Val806fs)]

NM_000527.5(LDLR):c.2416dup (p.Val806fs)

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.2416dup (p.Val806fs)

Other names:

NM_000527.5(LDLR):c.2416dup; p.Val806fs

HGVS:

NC_000019.10:g.11129539dup
NG_009060.1:g.45159dup
NM_000527.5:c.2416dupMANE SELECT
NM_001195798.2:c.2416dup
NM_001195799.2:c.2293dup
NM_001195800.2:c.1912dup
NM_001195803.2:c.1882dup
NP_000518.1:p.Val806fs
NP_001182727.1:p.Val806fs
NP_001182728.1:p.Val765fs
NP_001182729.1:p.Val638fs
NP_001182732.1:p.Val628fs
LRG_274:g.45159dup
NC_000019.10:g.11129539_11129540insG
NC_000019.9:g.11240210_11240211insG
NC_000019.9:g.11240215dup
NM_000527.4:c.2416dupG
NM_000527.5:c.2416dup
c.2416dupG
p.Val806Glyfs*11

Protein change:

V628fs

Links:

LDLR-LOVD, British Heart Foundation: LDLR_000304;

Molecular consequence:

NM_000527.5:c.2416dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.2416dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.2293dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.1912dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195803.2:c.1882dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens fibrinogen beta chain (FGB), transcript variant 1, mRNA
Homo sapiens fibrinogen beta chain (FGB), transcript variant 1, mRNA
gi|1813771595|ref|NM_005141.5|

Nucleotide
GPX7 [Chlorocebus sabaeus]
GPX7 [Chlorocebus sabaeus]
Gene ID:103224807

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568526	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 30, 2022)	germline	clinical testing	Citation Link,
SCV001134261	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Feb 16, 2019)	unknown	clinical testing	PubMed (14) [See all records that cite these PMIDs] 29213121, 31491741, 32041611, 32331935, 32770674, 33303402, 33418990, 33599434, 33740630, 34037665, 9767373, 10611908, 27816806, 26467025
SCV001926010	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001963348	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing

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Summary from all submissions

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

Citations

PubMed

The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian Population.

Fairoozy RH, Futema M, Vakili R, Abbaszadegan MR, Hosseini S, Aminzadeh M, Zaeri H, Mobini M, Humphries SE, Sahebkar A.

Sci Rep. 2017 Dec 6;7(1):17087. doi: 10.1038/s41598-017-17181-9.

PubMed [citation]

PMID:: 29213121
PMCID:: PMC5719081

Impact of LDLR and PCSK9 pathogenic variants in Japanese heterozygous familial hypercholesterolemia patients.

Hori M, Ohta N, Takahashi A, Masuda H, Isoda R, Yamamoto S, Son C, Ogura M, Hosoda K, Miyamoto Y, Harada-Shiba M.

Atherosclerosis. 2019 Oct;289:101-108. doi: 10.1016/j.atherosclerosis.2019.08.004. Epub 2019 Aug 19.

PubMed [citation]

PMID:: 31491741

See all PubMed Citations (14)

Details of each submission

From GeneDx, SCV000568526.5

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

Description

Identified in multiple individuals from various ethnic backgrounds with a diagnosis of FH in the published literature (Ekstrm et al., 1998; Nobe et al., 1999; Fouchier et al., 2001; Liguori et al., 2001; Yu et al., 2002; Kuhrov et al., 2002; Miyake et al., 2009; Ajmal et al., 2010; Dukov et al., 2011; Bertolini et al., 2013; Jannes et al., 2015; Khera et al., 2016; Setia et al., 2016; Xiang et al., 2017; Fairoozy et al., 2017; Trinder et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also known as c.785insG, c.2411insG, and c.2416_2417insG; This variant is associated with the following publications: (PMID: 23375686, 25846081, 11317362, 23535506, 11810272, 29213121, 25461735, 11754108, 10611908, 20217239, 18718593, 27050191, 21310417, 25682442, 28235710, 12417285, 27816806, 28994502, 31491741, 31345425, 32041611, 33303402, 32770674, 34037665, 33740630, 33418990, 33599434, 32331935, 9767373)

#	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		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001134261.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (14)

Description

This variant alters the translational reading frame of the LDLR mRNA and causes the premature termination of LDLR protein synthesis. This variant has been reported individuals with familial hypercholesterolemia (PMIDs: 27816806 (2016), 10611908 (1999), and 9767373 (1998)). Therefore, this variant is classified as pathogenic.

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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001926010.1

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

#	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		not provided	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001963348.1

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

#	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		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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