NM_000527.5(LDLR):c.981C>A (p.His327Gln) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 28, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000455675.2

Allele description [Variation Report for NM_000527.5(LDLR):c.981C>A (p.His327Gln)]

NM_000527.5(LDLR):c.981C>A (p.His327Gln)

Gene:
LDLR:low density lipoprotein receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_000527.5(LDLR):c.981C>A (p.His327Gln)
Other names:
NM_000527.5(LDLR):c.981C>A
HGVS:
  • NC_000019.10:g.11110692C>A
  • NG_009060.1:g.26312C>A
  • NM_000527.5:c.981C>AMANE SELECT
  • NM_001195798.2:c.981C>A
  • NM_001195799.2:c.858C>A
  • NM_001195800.2:c.477C>A
  • NM_001195803.2:c.600C>A
  • NP_000518.1:p.His327Gln
  • NP_000518.1:p.His327Gln
  • NP_001182727.1:p.His327Gln
  • NP_001182728.1:p.His286Gln
  • NP_001182729.1:p.His159Gln
  • NP_001182732.1:p.His200Gln
  • LRG_274t1:c.981C>A
  • LRG_274:g.26312C>A
  • LRG_274p1:p.His327Gln
  • NC_000019.9:g.11221368C>A
  • NM_000527.4:c.981C>A
Protein change:
H159Q
Links:
dbSNP: rs1060499933
NCBI 1000 Genomes Browser:
rs1060499933
Molecular consequence:
  • NM_000527.5:c.981C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.981C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195799.2:c.858C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.477C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.600C>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000540908Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 27, 2017) 		unknownclinical testing

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

SCV004022471ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

(ClinGen FH ACMG Specifications v1-2)		Uncertain significance
(Apr 28, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
Caucasianunknownyes11not provided3976not 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 Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, SCV000540908.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes3976Whole bloodnot provided1not provided1not provided

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV004022471.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.981C>A (p.His327Gln) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PP4 - Variant meets PM2. Identified in 1 FH case from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation) (Czechia) with Simon-Broome possible FH, after alternative causes of high cholesterol were excluded.

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

Last Updated: Oct 20, 2024