Variant: NM_000527.5(LDLR):c.91G>A (p.Glu31Lys)

CA041752

251013 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 47029d08-db26-42fe-bf8b-bcd8c066753d

Approved on: 2023-03-24

Published on: 2025-04-23

HGVS expressions

NM_000527.5:c.91G>A
NM_000527.5(LDLR):c.91G>A (p.Glu31Lys)
NC_000019.10:g.11100246G>A
CM000681.2:g.11100246G>A
NC_000019.9:g.11210922G>A
CM000681.1:g.11210922G>A
NC_000019.8:g.11071922G>A
NG_009060.1:g.15866G>A
ENST00000252444.10:c.349G>A
ENST00000559340.2:c.91G>A
ENST00000560467.2:c.91G>A
ENST00000558518.6:c.91G>A
ENST00000252444.9:c.345G>A
ENST00000455727.6:c.91G>A
ENST00000535915.5:c.91G>A
ENST00000545707.5:c.91G>A
ENST00000557933.5:c.91G>A
ENST00000557958.1:n.177G>A
ENST00000558013.5:c.91G>A
ENST00000558518.5:c.91G>A
ENST00000560502.5:n.177G>A
NM_000527.4:c.91G>A
NM_001195798.1:c.91G>A
NM_001195799.1:c.91G>A
NM_001195800.1:c.91G>A
NM_001195803.1:c.91G>A
NM_001195798.2:c.91G>A
NM_001195799.2:c.91G>A
NM_001195800.2:c.91G>A
NM_001195803.2:c.91G>A

Uncertain Significance

• Met criteria codes: PM2 PP3

• Not Met criteria codes: PVS1 BA1 PM6 PM3 PM1 PM4 PM5 BS4 BS3 BS1 BS2 BP7 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PP4 PP1 PP2

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

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.91G>A (p.Glu31Lys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2023. The supporting evidence is as follows: PM2: PopMax MAF = 0.00005 (0.005%) in European (Non-Finnish) exomes (gnomAD v2.1.1). PP3: REVEL = 0.777.

Met criteria codes

• PM2: PopMax MAF = 0.00005 (0.005%) in European (Non-Finnish) exomes (gnomAD v 2.1.1).
• PP3: REVEL = 0.777, this is greater than 0.75.

Not Met criteria codes

• PVS1: Not a null variant.
• BA1: Not met.
• PM6: Not met.
• PM3: Not met.
• PM1: Not located in exon 4.
• PM4: Not an in-frame insertion/deletion.
• PM5: Not met.
• BS4: Not met.
• BS3: Not met.
• BS1: Not met.
• BS2: Not met.
• BP7: Not a synonymous variant.
• BP2: Not met.
• BP3: Not applicable
• BP4: REVEL = 0.777
• BP1: Not applicable
• PS2: Not met.
• PS4: Variant has been described in several publications (PMID 20145306, 34428338, 35910211), however, clinical criteria not met for identified probands.
• PS3: Not met.
• PS1: Not met.
• PP4: Clinical criterial not met on patients.
• PP1: Not met.
• PP2: Not applicable