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.1460A>G (p.Asn487Ser)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585464

251855 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 6576e33a-04d6-4dcb-8324-0ba2571b660b

Approved on: 2025-02-20

Published on: 2025-06-11

HGVS expressions

NM_000527.5:c.1460A>G

NM_000527.5(LDLR):c.1460A>G (p.Asn487Ser)

NC_000019.10:g.11113636A>G

CM000681.2:g.11113636A>G

NC_000019.9:g.11224312A>G

CM000681.1:g.11224312A>G

NC_000019.8:g.11085312A>G

NG_009060.1:g.29256A>G

ENST00000252444.10:c.1718A>G

ENST00000559340.2:c.1460A>G

ENST00000560467.2:c.1340A>G

ENST00000558518.6:c.1460A>G

ENST00000252444.9:c.1714A>G

ENST00000455727.6:c.956A>G

ENST00000535915.5:c.1337A>G

ENST00000545707.5:c.1079A>G

ENST00000557933.5:c.1460A>G

ENST00000558013.5:c.1460A>G

ENST00000558518.5:c.1460A>G

ENST00000559340.1:c.181A>G

NM_000527.4:c.1460A>G

NM_001195798.1:c.1460A>G

NM_001195799.1:c.1337A>G

NM_001195800.1:c.956A>G

NM_001195803.1:c.1079A>G

NM_001195798.2:c.1460A>G

NM_001195799.2:c.1337A>G

NM_001195800.2:c.956A>G

NM_001195803.2:c.1079A>G

Uncertain Significance

PP4 PP3 PM2

PS4

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.1460A>G (p.Asn487Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 20 February 2025. The supporting evidence is as follows: PM2: PopMax MAF = 0.0000008475 (0.00008475%) in European (non-Finnish) genomes (gnomAD v4.1.0). PP3: REVEL = 0.802. PP4: Variant meets PM2 and is identified in at least 1 index case (1 case with possible FH by Simon Broome criteria from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, France), after alternative causes of high cholesterol were excluded.

PP4

Variant meets PM2 and is identified in at least 1 index case who fulfills SB possible criteria for FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des, Dyslipidémies, after alternative causes of high cholesterol were excluded.

PP3

REVEL = 0.802.

PM2

PopMax MAF = 0.0000008475 (0.00008475%) in European (non-Finnish) genomes (gnomAD v4.1.0).

PS4

Variant was found in a single FH proband (Simon Broome possible; Centre de Génétique Moléculaire et Chromosomique)

Curation History

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