NM_000527.5(LDLR):c.379del (p.Val127fs) AND Familial hypercholesterolemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 10, 2016
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:: RCV001382356.6

Allele description [Variation Report for NM_000527.5(LDLR):c.379del (p.Val127fs)]

NM_000527.5(LDLR):c.379del (p.Val127fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_000527.5(LDLR):c.379del (p.Val127fs)

HGVS:

NC_000019.10:g.11105285del
NG_009060.1:g.20905del
NM_000527.5:c.379delMANE SELECT
NM_001195798.2:c.379del
NM_001195799.2:c.256del
NM_001195800.2:c.314-2107del
NM_001195803.2:c.314-1280del
NP_000518.1:p.Val127fs
NP_001182727.1:p.Val127fs
NP_001182728.1:p.Val86fs
LRG_274:g.20905del
NC_000019.9:g.11215961del
NC_000019.9:g.11215961delG
NM_000527.4:c.379delG

Protein change:

V127fs

Links:

dbSNP: rs878854028

NCBI 1000 Genomes Browser:

rs878854028

Molecular consequence:

NM_000527.5:c.379del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195798.2:c.379del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195799.2:c.256del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001195800.2:c.314-2107del - intron variant - [Sequence Ontology: SO:0001627]
NM_001195803.2:c.314-1280del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001581091	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 10, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20809525, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581091

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 10, 2016)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular spectrum of autosomal dominant hypercholesterolemia in France.

Marduel M, Carrié A, Sassolas A, Devillers M, Carreau V, Di Filippo M, Erlich D, Abifadel M, Marques-Pinheiro A, Munnich A, Junien C; French ADH Research Network., Boileau C, Varret M, Rabès JP.

Hum Mutat. 2010 Nov;31(11):E1811-24. doi: 10.1002/humu.21348.

PubMed [citation]

PMID:: 20809525
PMCID:: PMC3152176

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001581091.4

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

Description

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, truncating variants in LDLR are known to be pathogenic (PMID: 20809525). This sequence change deletes 1 nucleotide from exon 4 of the LDLR mRNA (c.379delG), causing a frameshift at codon 127. This creates a premature translational stop signal (p.Val127Serfs*79) and is expected to result in an absent or disrupted protein product.

#	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: Feb 20, 2024

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