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NM_000527.5(LDLR):c.226G>C (p.Gly76Arg) AND Hypercholesterolemia, familial, 1

Germline classification:
Uncertain significance (1 submission)
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:
RCV003318691.1

Allele description [Variation Report for NM_000527.5(LDLR):c.226G>C (p.Gly76Arg)]

NM_000527.5(LDLR):c.226G>C (p.Gly76Arg)

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.226G>C (p.Gly76Arg)
Other names:
NM_000527.5(LDLR):c.226G>C; p.Gly76Arg
HGVS:
  • NC_000019.10:g.11102699G>C
  • NG_009060.1:g.18319G>C
  • NM_000527.5:c.226G>CMANE SELECT
  • NM_001195798.2:c.226G>C
  • NM_001195799.2:c.190+2354G>C
  • NM_001195800.2:c.226G>C
  • NM_001195803.2:c.226G>C
  • NP_000518.1:p.Gly76Arg
  • NP_001182727.1:p.Gly76Arg
  • NP_001182729.1:p.Gly76Arg
  • NP_001182732.1:p.Gly76Arg
  • LRG_274t1:c.226G>C
  • LRG_274:g.18319G>C
  • NC_000019.9:g.11213375G>C
  • NM_000527.4:c.226G>C
Protein change:
G76R
Links:
dbSNP: rs574337291
NCBI 1000 Genomes Browser:
rs574337291
Molecular consequence:
  • NM_001195799.2:c.190+2354G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000527.5:c.226G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195798.2:c.226G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195800.2:c.226G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001195803.2:c.226G>C - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004022426ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel
reviewed by expert panel

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel, SCV004022426.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000527.5(LDLR):c.226G>C (p.Gly76Arg) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PS3_Moderate and PP3 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: PS3_Moderate: Level 2 assays: PMID 34970301: Heterologous cells (HEK-293), WB and CLSM assays - result: 63% uptake. Result it below 70% of wild-type, so PS3_Moderate is met. PP3: REVEL=0.83. It is above 0.75. So, PP3 is met.

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

Last Updated: Sep 1, 2024