Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.274C>G (p.Gln92Glu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA042636

251108 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 5056957d-745a-4de4-8f27-3bfb9c4cf7fc

Approved on: 2022-10-28

Published on: 2025-02-07

HGVS expressions

NM_000527.5:c.274C>G

NM_000527.5(LDLR):c.274C>G (p.Gln92Glu)

NC_000019.10:g.11102747C>G

CM000681.2:g.11102747C>G

NC_000019.9:g.11213423C>G

CM000681.1:g.11213423C>G

NC_000019.8:g.11074423C>G

NG_009060.1:g.18367C>G

ENST00000252444.10:c.532C>G

ENST00000559340.2:c.274C>G

ENST00000560467.2:c.274C>G

ENST00000558518.6:c.274C>G

ENST00000252444.9:c.528C>G

ENST00000455727.6:c.274C>G

ENST00000535915.5:c.190+2402C>G

ENST00000545707.5:c.274C>G

ENST00000557933.5:c.274C>G

ENST00000557958.1:n.360C>G

ENST00000558013.5:c.274C>G

ENST00000558518.5:c.274C>G

NM_000527.4:c.274C>G

NM_001195798.1:c.274C>G

NM_001195799.1:c.190+2402C>G

NM_001195800.1:c.274C>G

NM_001195803.1:c.274C>G

NM_001195798.2:c.274C>G

NM_001195799.2:c.190+2402C>G

NM_001195800.2:c.274C>G

NM_001195803.2:c.274C>G

Uncertain Significance

PP4 PM2 BP4

PP3 PM3 PM5 BS3 PS3 PS1

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.274C>G (p.Gln92Glu) variant is classified as a variant of Uncertain significance - conflicting evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP4, and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2022. The supporting evidence is as follows: PM2: PopMax MAF = 0.000008790 in European Non-Finnish exomes (gnomAD v2.1.1). BP4: REVEL = 0.49. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) variant is not on limits. B) variant does not create a de-novo AG or GT. The variant is not predicted to alter splicing. PP4: Variant meets PM2 and is identified in 1 case with possible FH by Simon Broome criteria from Cardiovascular Research group, Instituto Nacional de Saúde Doutor Ricardo Jorge, Portugal.

PP4

Variant meets PM2. Identified in 1 FH case from Cardiovascular Research Group with Simon Broome possible FH phenotype.

PM2

PopMax MAF = 0.000008790 in European Non-Finnish exomes (gnomAD v2.1.1)

BP4

REVEL = 0.49. It is not above 0.75, splicing evaluation needed. Functional data on splicing not available. A) variant is not on limits. B) variant does not create a de-novo AG or GT The variant is not predicted to alter splicing.

PP3

PM3

Phase is uncertain

PM5

No other missense variants on the same codon.

BS3

PMID: 34167030, uptake is 79% and not above 90%

PS3

PMID: 34167030, uptake is 79% and not below 70%.

PS1

No other missense variants on the same codon.

Curation History

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