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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000527.5(LDLR):c.1210A>C (p.Thr404Pro)

CA10585359

251735 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 893fa193-f63f-4fcd-b2be-1768f75bd99b

HGVS expressions

NM_000527.5:c.1210A>C

NM_000527.5(LDLR):c.1210A>C (p.Thr404Pro)

NC_000019.10:g.11113301A>C

CM000681.2:g.11113301A>C

NC_000019.9:g.11223977A>C

CM000681.1:g.11223977A>C

NC_000019.8:g.11084977A>C

NG_009060.1:g.28921A>C

ENST00000558518.6:c.1210A>C

ENST00000252444.9:n.1464A>C

ENST00000455727.6:c.706A>C

ENST00000535915.5:c.1087A>C

ENST00000545707.5:c.829A>C

ENST00000557933.5:c.1210A>C

ENST00000558013.5:c.1210A>C

ENST00000558518.5:c.1210A>C

ENST00000560173.1:n.209A>C

ENST00000560467.1:n.690A>C

NM_000527.4:c.1210A>C

NM_001195798.1:c.1210A>C

NM_001195799.1:c.1087A>C

NM_001195800.1:c.706A>C

NM_001195803.1:c.829A>C

NM_001195798.2:c.1210A>C

NM_001195799.2:c.1087A>C

NM_001195800.2:c.706A>C

NM_001195803.2:c.829A>C

Uncertain Significance

PP4 PP3 PM2

PS2 PS4 PS3 PS1 BP2 BP4 BP7 BA1 PP1 PM3 PM1 PM4 PM5 PVS1 PM6 BS2 BS4 BS3 BS1

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.1210A>C (p.Thr404Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP3, and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2: This variant is absent from gnomAD v2.1.1 PP3: REVEL= 0.93 PP4: Variant meets PM2 and is identified in at least 1 index case who fulfills SB definite criteria for FH from PMID 8697568, after alternative causes of high cholesterol were excluded.

PP4

Variant meets PM2 and is identified in at least 1 index case who fulfills SB definite criteria for FH from PMID 8697568, after alternative causes of high cholesterol were excluded.

PP3

REVEL= 0.93

PM2

This variant is absent from gnomAD v2.1.1

PS2

Not met.

PS4

Not met.

PS3

No Functional evidence.

PS1

Not met.

BP2

Not met.

BP4

REVEL= 0.93

BP7

Not a synonymous variant.

BA1

This variant is absent from gnomAD v2.1.1

PP1

Not met.

PM3

Not met.

PM1

Not located in exon 4 or at a cysteine residue.

PM4

Not an in-frame deletion or insertion.

PM5

Not met.

PVS1

Not met.

PM6

Not met.

BS2

Not met.

BS4

Not met.

BS3

No Functional evidence.

BS1

This variant is absent from gnomAD v2.1.1

Approved on: 2023-04-28

Published on: 2023-05-01

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