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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data

Variant: NM_000527.5(LDLR):c.1436T>C (p.Leu479Pro)

CA10585450

251840 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: d87f1422-663b-4da8-b728-a09fc3b7d839
Approved on: 2024-02-23
Published on: 2025-02-24

HGVS expressions

NM_000527.5:c.1436T>C
NM_000527.5(LDLR):c.1436T>C (p.Leu479Pro)
NC_000019.10:g.11113612T>C
CM000681.2:g.11113612T>C
NC_000019.9:g.11224288T>C
CM000681.1:g.11224288T>C
NC_000019.8:g.11085288T>C
NG_009060.1:g.29232T>C
ENST00000252444.10:c.1694T>C
ENST00000559340.2:c.1436T>C
ENST00000560467.2:c.1316T>C
ENST00000558518.6:c.1436T>C
ENST00000252444.9:c.1690T>C
ENST00000455727.6:c.932T>C
ENST00000535915.5:c.1313T>C
ENST00000545707.5:c.1055T>C
ENST00000557933.5:c.1436T>C
ENST00000558013.5:c.1436T>C
ENST00000558518.5:c.1436T>C
ENST00000559340.1:c.157T>C
ENST00000560467.1:c.916T>C
NM_000527.4:c.1436T>C
NM_001195798.1:c.1436T>C
NM_001195799.1:c.1313T>C
NM_001195800.1:c.932T>C
NM_001195803.1:c.1055T>C
NM_001195798.2:c.1436T>C
NM_001195799.2:c.1313T>C
NM_001195800.2:c.932T>C
NM_001195803.2:c.1055T>C
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Uncertain Significance

Met criteria codes 4
PP4 PP3 PM2 PS4_Supporting
Not Met criteria codes 18
BA1 BS2 BS4 BS3 BS1 BP7 BP2 BP4 PVS1 PS2 PS3 PS1 PP1 PM3 PM1 PM4 PM5 PM6

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1436T>C (p.Leu479Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3, PP4 and PS4_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. The supporting evidence is as follows: PM2: This variant is absent from gnomAD v4.0.0. PP3: REVEL= 0.949. PS4_Supporting, PP4: At least four unrelated index cases fulfil FH criteria: one reported in VCI with DLCN ≥6 from Robarts Research Institute, Canada; one case in ClinVar with probable FH by DLCNC reported from U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, France; at least one index case fulfils Simon Broome criteria, reported from UK in PMID 11313767 (Table 1), 16389549 (Table 2) and 20736250 (Table 1, Figure 1); at least one case reported in PMID 19318025 with DLCN ≥6 (Supplementary table B).
Met criteria codes
PP4
At least four unrelated index cases fulfil FH criteria: one reported in VCI from Robarts Research Institute fulfil DLCN≥6, one case in ClinVar reported from U4M fulfil DLCN probable FH with no secondary finding. At least one index case fulfils SB criteria, reported from UK in PMID 11313767 (Table 1), 16389549 (Table 2) and 20736250 (Table 1, Figure 1). At least one case reported in PMID 19318025 fulfils DLCN ≥6 (Supplementary table B).
PP3
REVEL= 0.949
PM2
This variant is absent from gnomAD v4.0.0
PS4_Supporting
At least four unrelated index cases fulfil FH criteria: one reported in VCI from Robarts Research Institute fulfil DLCN≥6, one case in ClinVar reported from U4M fulfil DLCN probable FH with no secondary finding. At least one index case fulfils SB criteria, reported from UK in PMID 11313767 (Table 1), 16389549 (Table 2) and 20736250 (Table 1, Figure 1). At least one case reported in PMID 19318025 fulfils DLCN ≥6 (Supplementary table B).
Not Met criteria codes
BA1
This variant is absent from gnomAD v2.1.1
BS2
Not met.
BS4
Not met.
BS3
No data available.
BS1
This variant is absent from gnomAD v2.1.1
BP7
Not a synonymous variant.
BP2
Not met.
BP4
REVEL= 0.949
PVS1
Not a null variant.
PS2
Not met.
PS3
No data available.
PS1
Not met.
PP1
Not met.
PM3
Not met.
PM1
Not located in exon 4 or at a cysteine residue.
PM4
Not an in-frame deletion/insertion.
PM5
Not met.
PM6
Not met.
Curation History
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