Evidence Repository
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
  • 'cspec' property is found but contains no ID!
  • See Evidence submitted by expert panel for details.

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

CA10585508

251903 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
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 3
PP4 PP3 PM2
Not Met criteria codes 23
PP1 PP2 BA1 PM6 PM3 PM1 PM4 PM5 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PVS1 PS2 PS4 PS3 PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
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
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
BA1
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
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
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
BS2
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
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
PVS1
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
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.