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
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.5(LDLR):c.491T>C (p.Leu164Pro)

CA10584944

251252 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: b5eb13cb-9372-480b-b8d2-b7a84848d57d
Approved on: 2024-02-23
Published on: 2024-09-25

HGVS expressions

NM_000527.5:c.491T>C
NM_000527.5(LDLR):c.491T>C (p.Leu164Pro)
NC_000019.10:g.11105397T>C
CM000681.2:g.11105397T>C
NC_000019.9:g.11216073T>C
CM000681.1:g.11216073T>C
NC_000019.8:g.11077073T>C
NG_009060.1:g.21017T>C
ENST00000252444.10:c.749T>C
ENST00000559340.2:c.491T>C
ENST00000560467.2:c.491T>C
ENST00000558518.6:c.491T>C
ENST00000252444.9:c.745T>C
ENST00000455727.6:c.314-1995T>C
ENST00000535915.5:c.368T>C
ENST00000545707.5:c.314-1168T>C
ENST00000557933.5:c.491T>C
ENST00000558013.5:c.491T>C
ENST00000558518.5:c.491T>C
ENST00000560467.1:c.91T>C
NM_000527.4:c.491T>C
NM_001195798.1:c.491T>C
NM_001195799.1:c.368T>C
NM_001195800.1:c.314-1995T>C
NM_001195803.1:c.314-1168T>C
NM_001195798.2:c.491T>C
NM_001195799.2:c.368T>C
NM_001195800.2:c.314-1995T>C
NM_001195803.2:c.314-1168T>C

Uncertain Significance

Met criteria codes 3
PP3 PM2 PM1
Not Met criteria codes 19
PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 PS2 PS4 PS3 PS1 PP4 PP1 PM6 PM3 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.491T>C (p.Leu164Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1, PM2 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.801. PM1: Variant meets PM2 and is a missense in exon 4.
Met criteria codes
PP3
REVEL=0.801. It is >0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met.
PM1
Variant meets PM2 and it is exon 4 (codon 164). So, PM1 is met.
Not Met criteria codes
PVS1
Not a null variant (nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single or multiexon deletion)
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS2
No data available.
BS4
No data available.
BS3
No data available
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BP2
No data available.
BP3
No in-frame deletions/insertions
BP4
REVEL=0.801. It is >0.5.
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No data available.
PS3
No data available
PS1
No other missense variants in the same codon.
PP4
No data available.
PP1
No data available.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No data available.
PM4
No in-frame deletions/insertions
PM5
No other missense variants in the same codon.
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