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.905G>A (p.Cys302Tyr)

CA10585186

251515 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: 686d8d2d-402e-40b6-aa64-cb4121c3575d

Approved on: 2023-06-23

Published on: 2025-08-25

HGVS expressions

NM_000527.5(LDLR):c.905G>A (p.Cys302Tyr)

NM_000527.5:c.905G>A

NC_000019.10:g.11107479G>A

CM000681.2:g.11107479G>A

NC_000019.9:g.11218155G>A

CM000681.1:g.11218155G>A

NC_000019.8:g.11079155G>A

NG_009060.1:g.23099G>A

ENST00000252444.10:c.1163G>A

ENST00000559340.2:c.905G>A

ENST00000560467.2:c.905G>A

ENST00000558518.6:c.905G>A

ENST00000252444.9:c.1159G>A

ENST00000455727.6:c.401G>A

ENST00000535915.5:c.782G>A

ENST00000545707.5:c.524G>A

ENST00000557933.5:c.905G>A

ENST00000558013.5:c.905G>A

ENST00000558518.5:c.905G>A

ENST00000558528.1:n.420G>A

ENST00000560467.1:c.505G>A

NM_000527.4:c.905G>A

NM_001195798.1:c.905G>A

NM_001195799.1:c.782G>A

NM_001195800.1:c.401G>A

NM_001195803.1:c.524G>A

NM_001195798.2:c.905G>A

NM_001195799.2:c.782G>A

NM_001195800.2:c.401G>A

NM_001195803.2:c.524G>A

Likely Pathogenic

PP4 PP3 PM1 PM2 PS4_Supporting

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

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.905G>A (p.Cys302Tyr) variant is classified as Likely Pathogenic for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1, PM2, PP3, PP4 and PS4_Supporting 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= 0.98. PM1: Variant meets PM2 and alters Cys302, one of the cysteine residues listed. PS4_Supporting, PP4: Variant meets PM2 and is identified in 2 index cases who fulfill criteria for FH (Japan Atherosclerosis Society) from PMID 33461934 (Tada et al., 2021), after alternative causes of high cholesterol were excluded.

PP4

Variant meets PM2 and is identified in at least 1 index case who fulfills Japan Atherosclerosis Society criteria for FH from PMID 33461934, after alternative causes of high cholesterol were excluded.

PP3

REVEL= 0.98, 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)

PS4_Supporting

Variant meets PM2 and is identified in 2 index cases who fulfill Japan Atherosclerosis Society criteria for FH from PMID 33461934, after alternative causes of high cholesterol were excluded.

BP7

Not a synonymous variant.

BP2

No data.

BP4

REVEL = 0.98, this is greater than 0.50.

BS4

No data.

BS3

No data.

BS1

This variant is absent from gnomAD (gnomAD version 2.1.1)

BS2

No data.

PP1

No data.

PS2

Not met.

PS3

No data.

PS1

Variant meets criteria for PM1.

BA1

This variant is absent from gnomAD (gnomAD version 2.1.1)

PM3

No data.

PM4

Not an in-frame deletion/insertion.

PM5

Variant meets criteria for PM1.

PM6

Not met.

PVS1

Not a null variant.

Curation History

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