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]

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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

Approved on: 2023-04-28

Published on: 2023-05-01

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.

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