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.1825T>C (p.Phe609Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585632

252052 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 627e25c9-32f9-494c-bbbc-e0c679aa740d

Approved on: 2025-03-28

Published on: 2025-06-04

HGVS expressions

NM_000527.5:c.1825T>C

NM_000527.5(LDLR):c.1825T>C (p.Phe609Leu)

NC_000019.10:g.11116978T>C

CM000681.2:g.11116978T>C

NC_000019.9:g.11227654T>C

CM000681.1:g.11227654T>C

NC_000019.8:g.11088654T>C

NG_009060.1:g.32598T>C

ENST00000252444.10:c.2083T>C

ENST00000559340.2:c.1705+766T>C

ENST00000560467.2:c.1705T>C

ENST00000558518.6:c.1825T>C

ENST00000252444.9:c.2079T>C

ENST00000455727.6:c.1321T>C

ENST00000535915.5:c.1702T>C

ENST00000545707.5:c.1444T>C

ENST00000557933.5:c.1825T>C

ENST00000558013.5:c.1825T>C

ENST00000558518.5:c.1825T>C

ENST00000559340.1:c.426+766T>C

NM_000527.4:c.1825T>C

NM_001195798.1:c.1825T>C

NM_001195799.1:c.1702T>C

NM_001195800.1:c.1321T>C

NM_001195803.1:c.1444T>C

NM_001195798.2:c.1825T>C

NM_001195799.2:c.1702T>C

NM_001195800.2:c.1321T>C

NM_001195803.2:c.1444T>C

Uncertain Significance

PM2 PP4

BA1 BS4 BS3 BS1 BP4 PS4 PS3 PP1 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.1825T>C (p.Phe609Leu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying AMCG/AMP evidence codes PM2 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 March 2025. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v4.1.0). PP4: Variant meets PM2 and is identified in at least 1 index case fulfilling FH criteria, after alternative causes of high cholesterol were excluded, from PMID 16250003 (Fouchier et al., 2005).

PM2

This variant is absent from gnomAD (gnomAD v4.1).

PP4

Variant meets PM2 and is identified in at least 1 index case fulfilling FH criteria, after alternative causes of high cholesterol were excluded, from PMID:16250003

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS4

not met, (no information of index cases or report of segregation data/cases)

BS3

not met (no information or reports of functional data).

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP4

REVEL = 0.694. REVEL not above 0.75 and not bellow 0.50. Splicing evaluation is required. Functional data on splicing not available. A) not on limits; B) variant does not creates GT or AG; C) There is no AG or GT nearby. Variant is not predicted to alter splicing, so BP4 is not met.

PS4

not met, (no information of index cases or report of segregation data/cases)

PS3

not met (no information or reports of functional data).

PP1

not met, (no information of index cases or report of segregation data/cases)

PP3

Curation History

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