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NM_000527.5(LDLR):c.292G>A (p.Gly98Ser) AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 1, 2023
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:
RCV001177872.6

Allele description [Variation Report for NM_000527.5(LDLR):c.292G>A (p.Gly98Ser)]

NM_000527.5(LDLR):c.292G>A (p.Gly98Ser)

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.292G>A (p.Gly98Ser)
HGVS:
  • NC_000019.10:g.11102765G>A
  • NG_009060.1:g.18385G>A
  • NM_000527.5:c.292G>AMANE SELECT
  • NM_001195798.2:c.292G>A
  • NM_001195799.2:c.190+2420G>A
  • NM_001195800.2:c.292G>A
  • NM_001195803.2:c.292G>A
  • NP_000518.1:p.Gly98Ser
  • NP_000518.1:p.Gly98Ser
  • NP_001182727.1:p.Gly98Ser
  • NP_001182729.1:p.Gly98Ser
  • NP_001182732.1:p.Gly98Ser
  • LRG_274t1:c.292G>A
  • LRG_274:g.18385G>A
  • LRG_274p1:p.Gly98Ser
  • NC_000019.9:g.11213441G>A
  • NM_000527.4:c.292G>A
  • c.292G>A
Protein change:
G98S
Links:
LDLR-LOVD, British Heart Foundation: LDLR_001032; dbSNP: rs750474121
NCBI 1000 Genomes Browser:
rs750474121
Molecular consequence:
  • NM_001195799.2:c.190+2420G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.292G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.292G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.292G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.292G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001342163Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 1, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002086361Natera, Inc.
no assertion criteria provided
Uncertain significance
(Feb 21, 2020) 		germlineclinical testing

Help

Summary from all submissions

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

Citations

PubMed

Update of the molecular basis of familial hypercholesterolemia in The Netherlands.

Fouchier SW, Kastelein JJ, Defesche JC.

Hum Mutat. 2005 Dec;26(6):550-6.

PubMed [citation]
PMID:
16250003

Analysis of LDLR variants from homozygous FH patients carrying multiple mutations in the LDLR gene.

Jiang L, Benito-Vicente A, Tang L, Etxebarria A, Cui W, Uribe KB, Pan XD, Ostolaza H, Yang SW, Zhou YJ, Martin C, Wang LY.

Atherosclerosis. 2017 Aug;263:163-170. doi: 10.1016/j.atherosclerosis.2017.06.014. Epub 2017 Jun 8.

PubMed [citation]
PMID:
28645073
See all PubMed Citations (6)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001342163.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This missense variant (also known as p.Gly77Ser in the mature protein) replaces glycine with serine at codon 98 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown that this variant does not impact LDLR binding, uptake, or localization (PMID: 28645073). This variant has been reported in individuals affected with familial hypercholesterolemia (PMID: 16250003, 28645073, 34456200, 34573395; Zhu et al 2017 DOI: 10.1016/j.ijcme.2017.01.004) and in an individual affected with premature myocardial infarction (PMID: 30637778). This variant has been identified in 10/282872 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

From Natera, Inc., SCV002086361.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024