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.-188C>T

CA10583771

237861 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 6cfb1b35-abb2-4ad9-a7bd-4c759d2ba98f

Approved on: 2022-08-26

Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.-188C>T

NM_000527.5(LDLR):c.-188C>T

NC_000019.10:g.11089361C>T

CM000681.2:g.11089361C>T

NC_000019.9:g.11200037C>T

CM000681.1:g.11200037C>T

NC_000019.8:g.11061037C>T

NG_009060.1:g.4981C>T

NR_163945.1:n.299G>A

Uncertain Significance

PP4 PM2 PS4_Supporting

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.-188C>T 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). PP4: Variant meets PM2 and is identified in >1 index cases who fulfil FH diagnostic criteria after alternative causes of high cholesterol were excluded. PS4_Supporting: Variant meets PM2 and is identified in 2 unrelated index cases who fulfil DLCN criteria for definite FH. One case submitted to ClinVar from U4M - Lille University & CHRU Lille, France; 1 case reported by Fouchier et al, 2005, from Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.

PP4

Variant meets PM2 and is identified in >1 index cases who fulfil FH diagnostic criteria 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 fulfil DLCN criteria for definite FH. One case submitted to ClinVar from U4M - Lille University & CHRU Lille, France; 1 case reported by Fouchier et al, 2005, from Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.

PS3

Functional data is not available.

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