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.508G>A (p.Asp170Asn)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA043768

224617 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 1fbd867a-ffe8-431e-b00f-d9f99709868c

Approved on: 2025-03-04

Published on: 2025-03-04

HGVS expressions

NM_000527.5:c.508G>A

NM_000527.5(LDLR):c.508G>A (p.Asp170Asn)

NC_000019.10:g.11105414G>A

CM000681.2:g.11105414G>A

NC_000019.9:g.11216090G>A

CM000681.1:g.11216090G>A

NC_000019.8:g.11077090G>A

NG_009060.1:g.21034G>A

ENST00000252444.10:c.766G>A

ENST00000559340.2:c.508G>A

ENST00000560467.2:c.508G>A

ENST00000558518.6:c.508G>A

ENST00000252444.9:c.762G>A

ENST00000455727.6:c.314-1978G>A

ENST00000535915.5:c.385G>A

ENST00000545707.5:c.314-1151G>A

ENST00000557933.5:c.508G>A

ENST00000558013.5:c.508G>A

ENST00000558518.5:c.508G>A

ENST00000560467.1:c.108G>A

NM_000527.4:c.508G>A

NM_001195798.1:c.508G>A

NM_001195799.1:c.385G>A

NM_001195800.1:c.314-1978G>A

NM_001195803.1:c.314-1151G>A

NM_001195798.2:c.508G>A

NM_001195799.2:c.385G>A

NM_001195800.2:c.314-1978G>A

NM_001195803.2:c.314-1151G>A

Uncertain Significance

PM2 PM1

PS4 PP4 PP3

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.508G>A (p.Asp170Asn) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1 and PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 4 March 2025. The supporting evidence is as follows: PM1: Variant meets PM2 and is missense in exon 4. PM2: PopMax MAF = 0.00006186 (0.006186%) in European (non-Finnish) exomes (gnomAD v4.1.0).

PM2

PopMax MAF = 0.00006186 (0.006186 %) in European (non-Finnish) exomes (gnomAD v4.1.0).

PM1

Variant meets PM2 and is missense in exon 4.

PS4

Although there are FH patients in the literature who are reported to carry this variant, none of these patients have their FH phenotype described specifically enough to meet PS4 as defined by the VCEP.

PP4

Although there are FH patients in the literature who are reported to carry this variant, none of these patients have their FH phenotype described specifically enough to meet PP4 as defined by the VCEP.

PP3

REVEL = 0.641. Splicing evaluation required.

Curation History

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