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.904T>C (p.Cys302Arg)

CA404081019

440611 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: bcab7d84-27ed-49e7-9cc2-1691afb8d508

Approved on: 2023-06-23

Published on: 2025-10-29

HGVS expressions

NM_000527.5(LDLR):c.904T>C (p.Cys302Arg)

NM_000527.5:c.904T>C

NC_000019.10:g.11107478T>C

CM000681.2:g.11107478T>C

NC_000019.9:g.11218154T>C

CM000681.1:g.11218154T>C

NC_000019.8:g.11079154T>C

NG_009060.1:g.23098T>C

ENST00000252444.10:c.1162T>C

ENST00000559340.2:c.904T>C

ENST00000560467.2:c.904T>C

ENST00000558518.6:c.904T>C

ENST00000252444.9:c.1158T>C

ENST00000455727.6:c.400T>C

ENST00000535915.5:c.781T>C

ENST00000545707.5:c.523T>C

ENST00000557933.5:c.904T>C

ENST00000558013.5:c.904T>C

ENST00000558518.5:c.904T>C

ENST00000558528.1:n.419T>C

ENST00000560467.1:c.504T>C

NM_000527.4:c.904T>C

NM_001195798.1:c.904T>C

NM_001195799.1:c.781T>C

NM_001195800.1:c.400T>C

NM_001195803.1:c.523T>C

NM_001195798.2:c.904T>C

NM_001195799.2:c.781T>C

NM_001195800.2:c.400T>C

NM_001195803.2:c.523T>C

Uncertain Significance

PP3 PM1 PM2

BA1 BS2 BS4 BS3 BS1 BP2 BP4 PVS1 BP7 PS2 PS4 PS3 PS1 PP4 PP1 PM3 PM4 PM5 PM6

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.904T>C (p.Cys302Arg) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1, PM2 and PP3 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 version 2.1.1). PP3: REVEL = 0.972. PM1: Variant meets PM2 and alters Cys302, one of the cysteine residues listed.

PP3

REVEL = 0.972, this is greater than 0.75.

PM1

Variant meets PM2 and alters Cys302, one of the cysteine residues listed.

PM2

This variant is absent from gnomAD (gnomAD version 2.1.1).

BA1

This variant is absent from gnomAD (gnomAD version 2.1.1).

BS2

No data.

BS4

No data.

BS3

No data.

BS1

This variant is absent from gnomAD (gnomAD version 2.1.1).

BP2

No data.

BP4

REVEL = 0.972, this is greater than 0.50.

PVS1

Not a null variant.

BP7

Not a synonymous variant.

PS2

Not met.

PS4

No data.

PS3

No data.

PS1

Variant meets criteria for PM1.

PP4

No data.

PP1

No data.

PM3

No data.

PM4

Not an in-frame deletion/insertion.

PM5

Variant meets criteria for PM1.

PM6

Not met.

Curation History

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