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.590G>T (p.Cys197Phe)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA044039

251309 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 80471e75-a7c0-43b1-adbb-8e157b402631

Approved on: 2022-03-09

Published on: 2022-04-30

HGVS expressions

NM_000527.5:c.590G>T

NM_000527.5(LDLR):c.590G>T (p.Cys197Phe)

NC_000019.10:g.11105496G>T

CM000681.2:g.11105496G>T

NC_000019.9:g.11216172G>T

CM000681.1:g.11216172G>T

NC_000019.8:g.11077172G>T

NG_009060.1:g.21116G>T

ENST00000558518.6:c.590G>T

ENST00000252444.9:n.844G>T

ENST00000455727.6:c.314-1896G>T

ENST00000535915.5:c.467G>T

ENST00000545707.5:c.314-1069G>T

ENST00000557933.5:c.590G>T

ENST00000558013.5:c.590G>T

ENST00000558518.5:c.590G>T

ENST00000560467.1:n.190G>T

NM_000527.4:c.590G>T

NM_001195798.1:c.590G>T

NM_001195799.1:c.467G>T

NM_001195800.1:c.314-1896G>T

NM_001195803.1:c.314-1069G>T

NM_001195798.2:c.590G>T

NM_001195799.2:c.467G>T

NM_001195800.2:c.314-1896G>T

NM_001195803.2:c.314-1069G>T

Likely Pathogenic

PM1 PM2 PP4 PP3 PP1_Moderate

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.590G>T (p.Cys197Phe) variant is classified as likely pathogenic for Familial Hypercholesterolemia by applying evidence code PM1, PM2 PP1, PP3_Supporting 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 - PopMax MAF = 0.00006 (0.006%) in African exomes (gnomAD v2.1.1). PP3 - REVEL = 0.945. It is above 0.75 PM1 - Variant meets PM2 and located in highly conserved Cystein 197. PP1_Moderate - Variant segregate with phenotype in 4 informative meioses in 1 family. PP4 - Variant meets PM2 and is identified in 1 index case who fulfil SB criteria for FH (Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge)

PM1

Variant meets PM2 and located in highly conserved Cystein 197.

PM2

PopMax MAF = 0.00006 (0.006%) in African exomes (gnomAD v2.1.1).

PP4

Variant meets PM2 and is identified in 1 index case who fulfil SB criteria for FH (Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge)

PP3

REVEL = 0.945. It is above 0.75

PP1_Moderate

Variant segregate with phenotype in 4 informative meioses in 1 family.

Curation History

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