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.1796T>G (p.Leu599Trp)

CA10585617

252036 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 478cbf20-f7c0-4f4e-a000-1eb71b5e0c15

Approved on: 2022-08-29

Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.1796T>G

NM_000527.5(LDLR):c.1796T>G (p.Leu599Trp)

NC_000019.10:g.11116949T>G

CM000681.2:g.11116949T>G

NC_000019.9:g.11227625T>G

CM000681.1:g.11227625T>G

NC_000019.8:g.11088625T>G

NG_009060.1:g.32569T>G

ENST00000558518.6:c.1796T>G

ENST00000252444.9:n.2050T>G

ENST00000455727.6:c.1292T>G

ENST00000535915.5:c.1673T>G

ENST00000545707.5:c.1415T>G

ENST00000557933.5:c.1796T>G

ENST00000558013.5:c.1796T>G

ENST00000558518.5:c.1796T>G

ENST00000559340.1:n.426+737T>G

NM_000527.4:c.1796T>G

NM_001195798.1:c.1796T>G

NM_001195799.1:c.1673T>G

NM_001195800.1:c.1292T>G

NM_001195803.1:c.1415T>G

NM_001195798.2:c.1796T>G

NM_001195799.2:c.1673T>G

NM_001195800.2:c.1292T>G

NM_001195803.2:c.1415T>G

Uncertain Significance

PP4 PM2

PP3 BP4

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.1796T>G (p.Leu599Trp) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PS4_Supporting, PM2 and PP4 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) PP4 - Variant meets PM2 and is identified in at least 1 index case who fulfills SB possible/definite FH criteria for FH from PMID 22881376., after alternative causes of high cholesterol were excluded.

PP4

Variant meets PM2 and is identified in at least 1 index case who fulfills SB possible/definite FH criteria for FH from PMID 22881376., after alternative causes of high cholesterol were excluded.

PM2

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

PP3

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

BP4

REVEL = >0.5

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