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]

Variant: NM_000527.5(LDLR):c.2215C>T (p.Gln739Ter)

CA10585809

252258 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: c4ca2e41-d963-4724-bc04-e9367a9c883c

Approved on: 2022-08-29

Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.2215C>T

NM_000527.5(LDLR):c.2215C>T (p.Gln739Ter)

NC_000019.10:g.11123248C>T

CM000681.2:g.11123248C>T

NC_000019.9:g.11233924C>T

CM000681.1:g.11233924C>T

NC_000019.8:g.11094924C>T

NG_009060.1:g.38868C>T

ENST00000558518.6:c.2215C>T

ENST00000252444.9:n.2469C>T

ENST00000455727.6:c.1711C>T

ENST00000535915.5:c.2092C>T

ENST00000545707.5:c.1681C>T

ENST00000557933.5:c.2215C>T

ENST00000558013.5:c.2215C>T

ENST00000558518.5:c.2215C>T

NM_000527.4:c.2215C>T

NM_001195798.1:c.2215C>T

NM_001195799.1:c.2092C>T

NM_001195800.1:c.1711C>T

NM_001195803.1:c.1681C>T

NM_001195798.2:c.2215C>T

NM_001195799.2:c.2092C>T

NM_001195800.2:c.1711C>T

NM_001195803.2:c.1681C>T

Pathogenic

PVS1 PM2 PP4

PS4 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.2215C>T (p.Gln739Ter) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence code PVS1, 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). PVS1 - Stop in codon 739. It is upstream of amino acid 830. PP4 - Variant meets PM2 and is identified in one index case who fulfill FH/DLCN>=6 criteria for FH from Robarts Research Institute after alternative causes of high cholesterol were excluded.

PVS1

Stop in codon 739. It is upstream of amino acid 830.

PM2

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

PP4

Variant meets PM2 and is identified in one index case who fulfill FH/DLCN>=6 criteria for FH from Robarts Research Institute after alternative causes of high cholesterol were excluded.

PS4

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

PS3

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

Curation History

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