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.1078G>C (p.Asp360His)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA031936

523715 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 3069eaa8-ff46-4d72-b52d-f001660c7fc6

Approved on: 2024-10-28

Published on: 2025-01-19

HGVS expressions

NM_000527.5:c.1078G>C

NM_000527.5(LDLR):c.1078G>C (p.Asp360His)

NC_000019.10:g.11111531G>C

CM000681.2:g.11111531G>C

NC_000019.9:g.11222207G>C

CM000681.1:g.11222207G>C

NC_000019.8:g.11083207G>C

NG_009060.1:g.27151G>C

ENST00000252444.10:c.1336G>C

ENST00000559340.2:c.1078G>C

ENST00000560467.2:c.958G>C

ENST00000558518.6:c.1078G>C

ENST00000252444.9:c.1332G>C

ENST00000455727.6:c.574G>C

ENST00000535915.5:c.955G>C

ENST00000545707.5:c.697G>C

ENST00000557933.5:c.1078G>C

ENST00000558013.5:c.1078G>C

ENST00000558518.5:c.1078G>C

ENST00000560173.1:n.77G>C

ENST00000560467.1:c.558G>C

NM_000527.4:c.1078G>C

NM_001195798.1:c.1078G>C

NM_001195799.1:c.955G>C

NM_001195800.1:c.574G>C

NM_001195803.1:c.697G>C

NM_001195798.2:c.1078G>C

NM_001195799.2:c.955G>C

NM_001195800.2:c.574G>C

NM_001195803.2:c.697G>C

Uncertain Significance

BS1 BP4 PM5 PM2 PS1 BA1 PP4 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.1078G>C (p.Asp360His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying no ACMG/AMP evidence codes as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2024.

BS1

FAF = 0.0008704 (0.08704%) in Admixed American exomes (gnomAD v4.1.0).

BP4

REVEL = 0.549. It is not below 0.5.

PM5

1 other missense variants in the same codon: -NM_000527.5(LDLR):c.1080T>G (p.Asp360Glu) (ClinVar ID 440624) - Uncertain Significance by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines.

PM2

PopMax MAF = 0.0009337 (0.09337%) in Admixed American exomes+genomes (gnomAD v4.1.0).

PS1

There are no variants causing the same amino acid change classified as Pathogenic by these guidelines.

BA1

FAF = 0.0008704 (0.08704%) in Admixed American exomes (gnomAD v4.1.0).

PP4

Variant does not meet PM2.

PP3

REVEL= 0.549 Functional data on splicing not available, splicing evaluation needed. A) not on limits B) does not create GT/AG Variant is not predicted to alter splicing.

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.