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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.1244A>T (p.Asp415Val)

CA10585373

251750 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 1917847c-1383-4ebb-9c3d-b2954f97e777
Approved on: 2023-06-23
Published on: 2025-06-30

HGVS expressions

NM_000527.5:c.1244A>T
NM_000527.5(LDLR):c.1244A>T (p.Asp415Val)
NC_000019.10:g.11113335A>T
CM000681.2:g.11113335A>T
NC_000019.9:g.11224011A>T
CM000681.1:g.11224011A>T
NC_000019.8:g.11085011A>T
NG_009060.1:g.28955A>T
ENST00000252444.10:c.1502A>T
ENST00000559340.2:c.1244A>T
ENST00000560467.2:c.1124A>T
ENST00000558518.6:c.1244A>T
ENST00000252444.9:c.1498A>T
ENST00000455727.6:c.740A>T
ENST00000535915.5:c.1121A>T
ENST00000545707.5:c.863A>T
ENST00000557933.5:c.1244A>T
ENST00000558013.5:c.1244A>T
ENST00000558518.5:c.1244A>T
ENST00000560173.1:n.243A>T
ENST00000560467.1:c.724A>T
NM_000527.4:c.1244A>T
NM_001195798.1:c.1244A>T
NM_001195799.1:c.1121A>T
NM_001195800.1:c.740A>T
NM_001195803.1:c.863A>T
NM_001195798.2:c.1244A>T
NM_001195799.2:c.1121A>T
NM_001195800.2:c.740A>T
NM_001195803.2:c.863A>T
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Uncertain Significance

Met criteria codes 3
PP3 PM2 PM3
Not Met criteria codes 1
PM5

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1244A>T (p.Asp415Val) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM3 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 June 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL = 0.929. PM3: 1 case reported in PMID 36325061 (Du et al., 2022), China, who was homozygous and presented with an untreated LDL-C ≥13 mmol/L or a treated LDL-C ≥8 mmol/L and either cutaneous or tendon xanthomas before the age of 10 years.
Met criteria codes
PP3
- PP3: REVEL = 0.929. It is above 0.75, so PP3 is met.
PM2
- PM2: This variant is absent from gnomAD (gnomAD v2.1.1).
PM3
- PM3: 1 case reported in PMID 36325061, who is true homozygous and presents an untreated LDL-C ≥ 13 mmol/L or a treated LDL-C ≥ 8 mmol/L, either cutaneous or tendon xanthomas before the age of 10 years. PM3 is met.
Not Met criteria codes
PM5
NM_000527.5(LDLR):c.1244A>G (p.Asp415Gly) (ClinVar ID: 251749) considered as Likely Pathogenic by these guidelines. NM_000527.5(LDLR):c.1243G>C (p.Asp415His) (ClinVar ID: 251748) considered as Likely Pathogenic by these guidelines.
Curation History
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