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NM_000527.5(LDLR):c.932_933del (p.Lys311fs) AND Familial hypercholesterolemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 22, 2018
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:
RCV000775682.2

Allele description [Variation Report for NM_000527.5(LDLR):c.932_933del (p.Lys311fs)]

NM_000527.5(LDLR):c.932_933del (p.Lys311fs)

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.932_933del (p.Lys311fs)
HGVS:
  • NC_000019.10:g.11107506_11107507del
  • NG_009060.1:g.23126_23127del
  • NM_000527.5:c.932_933delMANE SELECT
  • NM_001195798.2:c.932_933del
  • NM_001195799.2:c.809_810del
  • NM_001195800.2:c.428_429del
  • NM_001195803.2:c.551_552del
  • NP_000518.1:p.Lys311fs
  • NP_001182727.1:p.Lys311fs
  • NP_001182728.1:p.Lys270fs
  • NP_001182729.1:p.Lys143fs
  • NP_001182732.1:p.Lys184fs
  • LRG_274:g.23126_23127del
  • NC_000019.9:g.11218181_11218182delAA
  • NC_000019.9:g.11218182_11218183del
  • NM_000527.4:c.932_933delAA
  • c.932_933del
  • p.Lys311Argfs*20
Protein change:
K143fs
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001869; dbSNP: rs879254723
NCBI 1000 Genomes Browser:
rs879254723
Molecular consequence:
  • NM_000527.5:c.932_933del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195798.2:c.932_933del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195799.2:c.809_810del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195800.2:c.428_429del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001195803.2:c.551_552del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000910089Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 22, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000910089.1

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

Description

Pathogenic variant based on current evidence: This variant deletes two nucleotides in exon 6 of the LDLR gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 9259195, 9727746). This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Truncating variants in the LDLR gene are known to be pathogenic (PMID: 20809525). Based on available evidence, this variant is classified as Pathogenic.

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

Last Updated: Sep 1, 2024