Variant: NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr)

CA10585508

251903 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 291d2666-6f2e-4024-918c-4640e9f5e5af

Approved on: 2022-01-18

Published on: 2022-06-30

HGVS expressions

NM_000527.5:c.1576C>A
NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr)
NC_000019.10:g.11113752C>A
CM000681.2:g.11113752C>A
NC_000019.9:g.11224428C>A
CM000681.1:g.11224428C>A
NC_000019.8:g.11085428C>A
NG_009060.1:g.29372C>A
ENST00000558518.6:c.1576C>A
ENST00000252444.9:n.1830C>A
ENST00000455727.6:c.1072C>A
ENST00000535915.5:c.1453C>A
ENST00000545707.5:c.1195C>A
ENST00000557933.5:c.1576C>A
ENST00000558013.5:c.1576C>A
ENST00000558518.5:c.1576C>A
ENST00000559340.1:n.297C>A
NM_000527.4:c.1576C>A
NM_001195798.1:c.1576C>A
NM_001195799.1:c.1453C>A
NM_001195800.1:c.1072C>A
NM_001195803.1:c.1195C>A
NM_001195798.2:c.1576C>A
NM_001195799.2:c.1453C>A
NM_001195800.2:c.1072C>A
NM_001195803.2:c.1195C>A

Uncertain Significance

• Met criteria codes: PP4 PP3 PM2

• Not Met criteria codes: BA1 BP2 BP3 BP4 BP1 BP5 BP7 BS2 BS4 BS3 BS1 PVS1 PP1 PP2 PM6 PS2 PS4 PS3 PS1 PM3 PM1 PM4 PM5

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.1576C>A (p.Pro526Thr) variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by applying evidence codes (PM2, 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 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.951. PP4 - Variant meets PM2. Identified in 1 FH case with clinical diagnosis of probable heterozygous hypercholesterolemia by DLCN score (DLCN = 8) from PMID 32770674.

Met criteria codes

• PP4: Variant meet PM2. PMID: 32770674 - 1 case who fulfills DLCN criteria for FH.
• PP3: REVEL = 0.951
• PM2: This variant is absent from gnomAD (gnomAD v2.1.1).

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline