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.300C>G (p.Asp100Glu)

CA404075813

440556 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 5b22ab46-ef1f-4e85-8364-cd407ae769e8

HGVS expressions

NM_000527.5:c.300C>G

NM_000527.5(LDLR):c.300C>G (p.Asp100Glu)

NC_000019.10:g.11102773C>G

CM000681.2:g.11102773C>G

NC_000019.9:g.11213449C>G

CM000681.1:g.11213449C>G

NC_000019.8:g.11074449C>G

NG_009060.1:g.18393C>G

ENST00000558518.6:c.300C>G

ENST00000252444.9:n.554C>G

ENST00000455727.6:c.300C>G

ENST00000535915.5:c.190+2428C>G

ENST00000545707.5:c.300C>G

ENST00000557933.5:c.300C>G

ENST00000557958.1:n.386C>G

ENST00000558013.5:c.300C>G

ENST00000558518.5:c.300C>G

NM_000527.4:c.300C>G

NM_001195798.1:c.300C>G

NM_001195799.1:c.190+2428C>G

NM_001195800.1:c.300C>G

NM_001195803.1:c.300C>G

NM_001195798.2:c.300C>G

NM_001195799.2:c.190+2428C>G

NM_001195800.2:c.300C>G

NM_001195803.2:c.300C>G

Uncertain Significance

PP4 PM2 PS4_Supporting

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.300C>G (p.Asp100Glu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP4, PS4_supporting 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 (gnomAD v2.1.1). PS4_supporting - Variant meets PM2 and is identified in 2 unrelated index cases who fulfill SB possible for FH from PMID 26361156. PP4 - Variant meets PM2 and is identified in 2 unrelated index cases who fulfill clinical criteria for FH from PMID 26361156, after alternative causes for high cholesterol were excluded

PP4

Variant meets PM2 and is identified in 2 unrelated index cases who fulfill SB possible for FH from PMID 26361156, after alternative causes of high cholesterol were excluded.

PM2

This variant is absent from gnomAD (gnomAD v2.1.1).

PS4_Supporting

Variant meets PM2 and is identified in 2 unrelated index cases who fulfill SB possible for FH from PMID 26361156.

PP3

REVEL score < 0.75, splicing assessed as well and not MET.

Approved on: 2023-04-28

Published on: 2023-05-01

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.