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.977C>G (p.Ser326Cys)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10585235

251581 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 68761f1c-ea68-4c34-8226-2b2de6723855

Approved on: 2022-04-05

Published on: 2022-04-05

HGVS expressions

NM_000527.5:c.977C>G

NM_000527.5(LDLR):c.977C>G (p.Ser326Cys)

NC_000019.10:g.11110688C>G

CM000681.2:g.11110688C>G

NC_000019.9:g.11221364C>G

CM000681.1:g.11221364C>G

NC_000019.8:g.11082364C>G

NG_009060.1:g.26308C>G

ENST00000558518.6:c.977C>G

ENST00000252444.9:n.1231C>G

ENST00000455727.6:c.473C>G

ENST00000535915.5:c.854C>G

ENST00000545707.5:c.596C>G

ENST00000557933.5:c.977C>G

ENST00000558013.5:c.977C>G

ENST00000558518.5:c.977C>G

ENST00000560467.1:n.541-826C>G

NM_000527.4:c.977C>G

NM_001195798.1:c.977C>G

NM_001195799.1:c.854C>G

NM_001195800.1:c.473C>G

NM_001195803.1:c.596C>G

NM_001195798.2:c.977C>G

NM_001195799.2:c.854C>G

NM_001195800.2:c.473C>G

NM_001195803.2:c.596C>G

Pathogenic

PM2 PP1_Strong PS4_Supporting PS3 PP4 PP3

BA1 BS4 BS1 BS3 BP4

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

PP1_strong: Variant segregates with FH phenotype in at least 28 informative meiosis (minimum 2) from 9 families from different labs (Laboratory of Genetics and Molecular Cardiology). PS3: PMID: 32015373. Level 1 assay. Heterologous cells (CHO), FACS assays. Normal cell surface LDLR (90%), 50% binding and 48% uptake. PS4_supporting: variant meets PM2 and is identified in 1 index case who fulfills SB criteria of definite FH from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation) and 1 index case with DLCN >6 from PMID 30270055, Corral et al., 2018 (Argentina) so PS4_Supporting is met PM2: No population data was found for this variant in gnomAD (gnomAD version 2.1.1). PP3: REVEL = 0.927. PP4: Variant meets PM2 and is identified in 1 index case who fulfils SB for FH from different labs (Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation) and Laboratory of Genetics and Molecular Cardiology).

PM2

No population data was found for this variant in gnomAD (gnomAD version 2.1.1).

PP1_Strong

Variant segregates with FH phenotype in at least 28 informative meiosis (minimum 2) from 9 families from different labs (Laboratory of Genetics and Molecular Cardiology).

PS4_Supporting

variant meets PM2 and is identified in 1 index case who fulfills SB criteria of definite FH from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation) and 1 index case with DLCN >6 from PMID 30270055, Corral et al., 2018 (Argentina) so PS4_Supporting is met.

PS3

PMID: 32015373. Level 1 assay. Heterologous cells (CHO), FACS assays. Normal cell surface LDLR (90%), 50% binding and 48% uptake.

PP4

Variant meets PM2 and is identified in 1 index case who fulfils SB for FH from different labs (Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation) and Laboratory of Genetics and Molecular Cardiology).

PP3

REVEL = 0.927.

BA1