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.1080T>G (p.Asp360Glu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA031958

440624 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 11a66486-f4d3-4363-ab30-6cf80fcc7826

Approved on: 2024-10-28

Published on: 2025-01-19

HGVS expressions

NM_000527.5:c.1080T>G

NM_000527.5(LDLR):c.1080T>G (p.Asp360Glu)

NC_000019.10:g.11111533T>G

CM000681.2:g.11111533T>G

NC_000019.9:g.11222209T>G

CM000681.1:g.11222209T>G

NC_000019.8:g.11083209T>G

NG_009060.1:g.27153T>G

ENST00000252444.10:c.1338T>G

ENST00000559340.2:c.1080T>G

ENST00000560467.2:c.960T>G

ENST00000558518.6:c.1080T>G

ENST00000252444.9:c.1334T>G

ENST00000455727.6:c.576T>G

ENST00000535915.5:c.957T>G

ENST00000545707.5:c.699T>G

ENST00000557933.5:c.1080T>G

ENST00000558013.5:c.1080T>G

ENST00000558518.5:c.1080T>G

ENST00000560173.1:n.79T>G

ENST00000560467.1:c.560T>G

NM_000527.4:c.1080T>G

NM_001195798.1:c.1080T>G

NM_001195799.1:c.957T>G

NM_001195800.1:c.576T>G

NM_001195803.1:c.699T>G

NM_001195798.2:c.1080T>G

NM_001195799.2:c.957T>G

NM_001195800.2:c.576T>G

NM_001195803.2:c.699T>G

Uncertain Significance

BP4

PS4 PS1 BA1 PP4 PP3 PM2 PM5 BS1 BP2

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.1080T>G (p.Asp360Glu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2024. The supporting evidence is as follows: BP4: REVEL = 0.404. it is below 0.50, so splicing evaluation is required. Functional data on splicing not available. A) not on limits B) it creates a de novo AG, but de novo score is below 0.8. Variant is not predicted to alter splicing.

BP4

REVEL = 0.404. it is below 0.50, so splicing evaluation is required. Functional data on splicing not available. A) not on limits B) it creates a de novo AG, but de novo score is below 0.8. Variant is not predicted to alter splicing.

PS4

Variant found in only 1 FH case

PS1

No variants causing the same amino acid change classified as Pathogenic by these guidelines.

BA1

FAF = 0.0001613 (0.01613%) in African/African American exomes (gnomAD v4.1.0).

PP4

Variant does not meet PM2

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

PopMax MAF = 0.0002269 (0.02269%) in African/African American exomes (gnomAD v4.1.0).

PM5

1 other missense variants in the same codon: - NM_000527.5(LDLR):c.1078G>C (p.Asp360His) (ClinVar ID 523715) - VUS by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines.

BS1

FAF = 0.0001613 (0.01613%) in African/African American exomes (gnomAD v4.1.0).

BP2

Could not determine whether these variants are in trans

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.