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NM_000527.5(LDLR):c.469_470dup (p.Ser157fs) AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 5, 2019
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:
RCV001044006.5

Allele description

NM_000527.5(LDLR):c.469_470dup (p.Ser157fs)

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.469_470dup (p.Ser157fs)
HGVS:
  • NC_000019.10:g.11105375_11105376dup
  • NG_009060.1:g.20995_20996dup
  • NM_000527.5:c.469_470dupMANE SELECT
  • NM_001195798.2:c.469_470dup
  • NM_001195799.2:c.346_347dup
  • NM_001195800.2:c.314-2017_314-2016dup
  • NM_001195803.2:c.314-1190_314-1189dup
  • NP_000518.1:p.Ser157fs
  • NP_001182727.1:p.Ser157fs
  • NP_001182728.1:p.Ser116fs
  • LRG_274t1:c.469_470dup
  • LRG_274:g.20995_20996dup
  • NC_000019.9:g.11216050_11216051insAG
  • NC_000019.9:g.11216051_11216052dup
  • NM_000527.4:c.469_470dup
Protein change:
S116fs
Links:
dbSNP: rs2077272442
NCBI 1000 Genomes Browser:
rs2077272442
Molecular consequence:
  • NM_000527.5:c.469_470dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195798.2:c.469_470dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195799.2:c.346_347dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195800.2:c.314-2017_314-2016dup - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001195803.2:c.314-1190_314-1189dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001207778Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Apr 5, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001207778.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Ser157Argfs*50) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LDLR-related conditions. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024