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.855C>A (p.His285Gln)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585161

251487 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: c502c288-a389-483f-9a54-fa159c47975c

Approved on: 2023-03-24

Published on: 2024-12-16

HGVS expressions

NM_000527.5:c.855C>A

NM_000527.5(LDLR):c.855C>A (p.His285Gln)

NC_000019.10:g.11107429C>A

CM000681.2:g.11107429C>A

NC_000019.9:g.11218105C>A

CM000681.1:g.11218105C>A

NC_000019.8:g.11079105C>A

NG_009060.1:g.23049C>A

ENST00000252444.10:c.1113C>A

ENST00000559340.2:c.855C>A

ENST00000560467.2:c.855C>A

ENST00000558518.6:c.855C>A

ENST00000252444.9:c.1109C>A

ENST00000455727.6:c.351C>A

ENST00000535915.5:c.732C>A

ENST00000545707.5:c.474C>A

ENST00000557933.5:c.855C>A

ENST00000558013.5:c.855C>A

ENST00000558518.5:c.855C>A

ENST00000558528.1:n.370C>A

ENST00000560467.1:c.455C>A

NM_000527.4:c.855C>A

NM_001195798.1:c.855C>A

NM_001195799.1:c.732C>A

NM_001195800.1:c.351C>A

NM_001195803.1:c.474C>A

NM_001195798.2:c.855C>A

NM_001195799.2:c.732C>A

NM_001195800.2:c.351C>A

NM_001195803.2:c.474C>A

Uncertain Significance

PM2

PM3 PM1 PM4 PM5 PM6 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP7 PS2 PS4 PS3 PS1 PVS1 PP4 PP1 PP3 PP2

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.855C>A (p.His285Gln) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2023. The supporting evidence is as follows: PM2: Variant absent from gnomAD (v2.1.1).

PM2

Variant absent from gnomAD (V2.1.1)

PM3

Not met.

PM1

Not located in exon 4 or at a cysteine residue.

PM4

Not an in-frame deletion/insertion.

PM5

Not met.

PM6

Not met.

BA1

Absent from gnomAD (V2.1.1)

BS2

Not met.

BS4

Not met.

BS3

Not met.

BS1

Absent from gnomAD (V2.1.1)

BP2

Not met.

BP3

Not applicable

BP4

REVEL= 0.591, this is not less than 0.50

BP1

Not applicable

BP7

Not a synonymous variant.

PS2

Not met.

PS4

Not met.

PS3

PMID: 27895090 Heterologous cells (549T cells from human fibroblasts), WB, FACS and 125I-LDL assays: "reduced rates of LDL accumulation but did not show defects in acid-dependent LDL release".

PS1

Not met.

PVS1

Not a null variant.

PP4

Not met. Reported in PMID 11851376 but insufficient detail on phenotype.

PP1

Not met.

PP3

REVEL= 0.591, this is not greater than 0.75 Variant is not predicted to alter splicing.

PP2

Not applicable

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.