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.1241T>G (p.Leu414Arg)

CA033186

251747 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: b468ce51-5ee8-474c-ba81-192f8484fa13

HGVS expressions

NM_000527.5:c.1241T>G

NM_000527.5(LDLR):c.1241T>G (p.Leu414Arg)

NC_000019.10:g.11113332T>G

CM000681.2:g.11113332T>G

NC_000019.9:g.11224008T>G

CM000681.1:g.11224008T>G

NC_000019.8:g.11085008T>G

NG_009060.1:g.28952T>G

ENST00000558518.6:c.1241T>G

ENST00000252444.9:n.1495T>G

ENST00000455727.6:c.737T>G

ENST00000535915.5:c.1118T>G

ENST00000545707.5:c.860T>G

ENST00000557933.5:c.1241T>G

ENST00000558013.5:c.1241T>G

ENST00000558518.5:c.1241T>G

ENST00000560173.1:n.240T>G

ENST00000560467.1:n.721T>G

NM_000527.4:c.1241T>G

NM_001195798.1:c.1241T>G

NM_001195799.1:c.1118T>G

NM_001195800.1:c.737T>G

NM_001195803.1:c.860T>G

NM_001195798.2:c.1241T>G

NM_001195799.2:c.1118T>G

NM_001195800.2:c.737T>G

NM_001195803.2:c.860T>G

Uncertain Significance

PS4_Supporting PP4 PP3 PM2

PS2 PS3 PS1 BP5 BP7 PVS1 BP2 BP3 BP4 BP1 BA1 PP1 PP2 PM6 PM3 PM1 PM4 PM5 BS4 BS3 BS1 BS2

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 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.1241T>G (p.Leu414Arg) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4_supporting, PP3 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 = 0.0001088 (0.01088%) in East Asian exomes+genomes (gnomAD v2.1.1). PP3 - REVEL = 0.822. PS4_supporting - Variant meets PM2. Variant identified in 4 unrelated index cases (3 cases with Simon-Broome published in PMID: 9763532; 1 case with DLCN criteria from Robarts Research Institute. PP4 - Variant meets PM2. Variant identified in 4 FH cases (3 cases with Simon-Broome Definite published in PMID: 9763532; 1 case with DLCN criteria = > 6 from Robarts Research Institute.

PS4_Supporting

Variant meets PM2. Variant identified in 4 unrelated index cases (3 cases with Simon-Broome published in PMID: 9763532; 1 case with DLCN criteria from Robarts Research Institute.

PP4

Variant meets PM2. Variant identified in 4 FH cases (3 cases with Simon-Broome Definite published in PMID: 9763532; 1 case with DLCN criteria = > 6 from Robarts Research Institute.

PP3

REVEL = 0.822

PM2

PopMax MAF = 0.0001088 (0.01088%) in East Asian exomes+genomes (gnomAD v2.1.1).

PS2