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.731C>G (p.Ser244Cys)

CA404079636

440599 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: 149c63e3-72b2-4878-86c5-64c191f9c0e1

Approved on: 2023-04-28

Published on: 2023-04-30

HGVS expressions

NM_000527.5:c.731C>G

NM_000527.5(LDLR):c.731C>G (p.Ser244Cys)

NC_000019.10:g.11106601C>G

CM000681.2:g.11106601C>G

NC_000019.9:g.11217277C>G

CM000681.1:g.11217277C>G

NC_000019.8:g.11078277C>G

NG_009060.1:g.22221C>G

ENST00000558518.6:c.731C>G

ENST00000252444.9:n.985C>G

ENST00000455727.6:c.314-791C>G

ENST00000535915.5:c.608C>G

ENST00000545707.5:c.350C>G

ENST00000557933.5:c.731C>G

ENST00000558013.5:c.731C>G

ENST00000558518.5:c.731C>G

ENST00000558528.1:n.246C>G

ENST00000560467.1:n.331C>G

NM_000527.4:c.731C>G

NM_001195798.1:c.731C>G

NM_001195799.1:c.608C>G

NM_001195800.1:c.314-791C>G

NM_001195803.1:c.350C>G

NM_001195798.2:c.731C>G

NM_001195799.2:c.608C>G

NM_001195800.2:c.314-791C>G

NM_001195803.2:c.350C>G

Uncertain Significance

PM2

BS2 PVS1 BS4 BS3 BS1 BP2 BP4 BP7 PS2 PS4 PS3 PS1 BA1 PP4 PP1 PP3 PM3 PM1 PM4 PM6

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 1.2

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.731C>G (p.Ser244Cys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 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: No exome data available for this variant in gnomAD v2.1.1. Genome and exome data were available for the neighboring variant, 19-11217264-G-A(GRCh37). The c.731C>G (p.Ser244Cys) variant was present in 1/15432 European (non-Finnish) genomes. The 19-11217264-G-A(GRCh37) variant was tested in 113760 alles from European (non-Finnish) exomes. Final adjusted allele frequency: 1/( 15432+ 113760) = 0.0007740417%.

PM2

No exome data available for this variant in gnomAD v2.1.1. Genome and exome data were available for the neighboring variant, 19-11217264-G-A(GRCh37). The c.731C>G (p.Ser244Cys) variant was present in 1/15432 European (non-Finnish) genomes. The 19-11217264-G-A(GRCh37) variant was tested in 113760 alleles from European (non-Finnish) exomes. Final adjusted allele frequency: 1/( 15432+ 113760) = 0.0007740417%.

BS2

Not met.

PVS1

Not met.

BS4

Not met.

BS3

Not met.

BS1

Not met.

BP2

Not met.

BP4

Not met.

BP7

Not met.

PS2

Not met.

PS4

Not met.

PS3

Not met.

PS1

Not met.

BA1

Not met.

PP4

Not met.

PP1

Not met.

PP3

Not met.

PM3

Not met.

PM1

Not met.

PM4

Not met.

PM6

Not met.

Curation History

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