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.1244A>G (p.Asp415Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585372

251749 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 6aafd8e9-dd32-4827-ac63-ea9349dd174e

Approved on: 2023-06-23

Published on: 2025-06-30

HGVS expressions

NM_000527.5:c.1244A>G

NM_000527.5(LDLR):c.1244A>G (p.Asp415Gly)

NC_000019.10:g.11113335A>G

CM000681.2:g.11113335A>G

NC_000019.9:g.11224011A>G

CM000681.1:g.11224011A>G

NC_000019.8:g.11085011A>G

NG_009060.1:g.28955A>G

ENST00000252444.10:c.1502A>G

ENST00000559340.2:c.1244A>G

ENST00000560467.2:c.1124A>G

ENST00000558518.6:c.1244A>G

ENST00000252444.9:c.1498A>G

ENST00000455727.6:c.740A>G

ENST00000535915.5:c.1121A>G

ENST00000545707.5:c.863A>G

ENST00000557933.5:c.1244A>G

ENST00000558013.5:c.1244A>G

ENST00000558518.5:c.1244A>G

ENST00000560173.1:n.243A>G

ENST00000560467.1:c.724A>G

NM_000527.4:c.1244A>G

NM_001195798.1:c.1244A>G

NM_001195799.1:c.1121A>G

NM_001195800.1:c.740A>G

NM_001195803.1:c.863A>G

NM_001195798.2:c.1244A>G

NM_001195799.2:c.1121A>G

NM_001195800.2:c.740A>G

NM_001195803.2:c.863A>G

Likely Pathogenic

PP4 PM2 PS4_Supporting PP1_Moderate

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.1244A>G (p.Asp415Gly) variant is classified as Likely Pathogenic, for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PS4_Moderate, PP1_Moderate and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 June 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PS4_Supporting, PP4: Variant meets PM2 and is identified in 2 unrelated cases who fulfill criteria for FH (at least 1 case from PMID 11810272 (Fouchier et al., 2001), The Netherlands; 1 case from PMID 10978268 (Bertolini et al., 2000), Italy). PP1_Moderate: Variant segregates with FH phenotype in at least 5 informative meiosis (minimum 4) from 1 family in PMID 10978268 (Bertolini et al., 2000), Italy.

PP4

- PP4: Variant meets PM2 and is identified in at least 1 index case fulfilling Simon-Broome criteria for (possible) FH, after alternative causes of high cholesterol are excluded from PMID: 11810272 and 10978268.

PM2

- PM2: This variant is absent from gnomAD (gnomAD v2.1.1).

PS4_Supporting

- PS4_Supporting: Variant meets PM2 and is identified in 2 unrelated cases who fulfiil specific criteria for FH: at least 1 index fulfilling Simon Broome criteria for definite or possible FH from PMID:11810272; and 1 index case fulfilling Simon Broome criteria from PMID:10978268.

PP1_Moderate

- PP1_Moderate: Variant segregates with FH phenotype in at least 5 informative meiosis (minimum 4) from 1 family from PMID: 10978268.

Curation History

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