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.1731G>C (p.Trp577Cys)

CA16615991

406163 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: f578d12a-f928-4f60-b8a2-95284f29565e

HGVS expressions

NM_000527.5:c.1731G>C

NM_000527.5(LDLR):c.1731G>C (p.Trp577Cys)

NC_000019.10:g.11116884G>C

CM000681.2:g.11116884G>C

NC_000019.9:g.11227560G>C

CM000681.1:g.11227560G>C

NC_000019.8:g.11088560G>C

NG_009060.1:g.32504G>C

ENST00000558518.6:c.1731G>C

ENST00000252444.9:n.1985G>C

ENST00000455727.6:c.1227G>C

ENST00000535915.5:c.1608G>C

ENST00000545707.5:c.1350G>C

ENST00000557933.5:c.1731G>C

ENST00000558013.5:c.1731G>C

ENST00000558518.5:c.1731G>C

ENST00000559340.1:n.426+672G>C

NM_000527.4:c.1731G>C

NM_001195798.1:c.1731G>C

NM_001195799.1:c.1608G>C

NM_001195800.1:c.1227G>C

NM_001195803.1:c.1350G>C

NM_001195798.2:c.1731G>C

NM_001195799.2:c.1608G>C

NM_001195800.2:c.1227G>C

NM_001195803.2:c.1350G>C

Uncertain Significance

PM2 PM5 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.1731G>C (p.Trp577Cys) variant is classified as uncertain significance for Familial Hypercholesterolemia by applying evidence codes PM2, PM5, PP3 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). PM5: 5 other missense variant(s) in the same codon, and 1 of them is classified as Pathogenic by these guidelines: - NM_000527.5(LDLR): variant (ClinVar ID 252000) PP3: REVEL = 0.939

PM2

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

PM5

5 other missense variant(s) in the same codon, and 1 of them is classified as Pathogenic by these guidelines: - NM_000527.5(LDLR): variant (ClinVar ID 252000)

PP3

REVEL = 0.939

Approved on: 2023-04-28

Published on: 2023-04-28

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