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_000527.4(LDLR):c.-101T>C

CA10584711

250957 (ClinVar)

Gene: N/A

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 0f55d8b6-db4f-49b1-bbc7-bdb13d5a3b02

HGVS expressions

NM_000527.4(LDLR):c.-101T>C

NC_000019.10:g.11089448T>C

CM000681.2:g.11089448T>C

NC_000019.9:g.11200124T>C

CM000681.1:g.11200124T>C

NC_000019.8:g.11061124T>C

NG_009060.1:g.5068T>C

ENST00000558518.5:c.-101T>C

NM_000527.4:c.-101T>C

NM_001195798.1:c.-101T>C

NM_001195799.1:c.-101T>C

NM_001195800.1:c.-101T>C

NM_001195803.1:c.-101T>C

NR_163945.1:n.212A>G

Uncertain Significance

PP4 PM2

PS3

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.-101T>C variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, 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 Met: This variant is absent in gnomAD (gnomAD v2.1.1). PP4 Met: Variant meets PM2 and is identified in 1 index case who fulfil Simon Broome criteria for FH diagnosis (British Heart Foundation Laboratories, Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences, University College London, London, UK, PMID 22881376). PS3 not met: Heterologous cells (Huh7) were used in luciferase assay (level 3 functional assay), and have shown 64% reporter gene expression, which is greater than 50% compared to wild-type (Khamis et al 2015, Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute Cardiovascular Science, University College London Medicine School, London, UK, PMID 25248394).

PP4

Variant meets PM2 and is identified in 1 index case who fulfil Simon Broome criteria for FH diagnosis (British Heart Foundation Laboratories, Centre for Cardiovascular Genetics, Institute of Cardiovascular Sciences, University College London, London, UK, PMID 22881376).

PM2

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

PS3

Heterologous cells (Huh7) were used in luciferase assay (level 3 functional assay), and have shown 64% reporter gene expression, which is greater than 50% compared to wild-type (Khamis et al 2015, Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Institute Cardiovascular Science, University College London Medicine School, London, UK, PMID 25248394).

Approved on: 2022-02-10

Published on: 2022-04-25

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