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 label mismatch: LDLR vs undefined
  • 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.1441G>A (p.Val481Met)

CA10585453

251843 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: e9fae1f3-84f4-4a1e-9c2f-fd89c9805ae0
Approved on: 2025-02-28
Published on: 2025-04-10

HGVS expressions

NM_000527.5:c.1441G>A
NM_000527.5(LDLR):c.1441G>A (p.Val481Met)
NC_000019.10:g.11113617G>A
CM000681.2:g.11113617G>A
NC_000019.9:g.11224293G>A
CM000681.1:g.11224293G>A
NC_000019.8:g.11085293G>A
NG_009060.1:g.29237G>A
ENST00000252444.10:c.1699G>A
ENST00000559340.2:c.1441G>A
ENST00000560467.2:c.1321G>A
ENST00000558518.6:c.1441G>A
ENST00000252444.9:c.1695G>A
ENST00000455727.6:c.937G>A
ENST00000535915.5:c.1318G>A
ENST00000545707.5:c.1060G>A
ENST00000557933.5:c.1441G>A
ENST00000558013.5:c.1441G>A
ENST00000558518.5:c.1441G>A
ENST00000559340.1:c.162G>A
ENST00000560467.1:c.921G>A
NM_000527.4:c.1441G>A
NM_001195798.1:c.1441G>A
NM_001195799.1:c.1318G>A
NM_001195800.1:c.937G>A
NM_001195803.1:c.1060G>A
NM_001195798.2:c.1441G>A
NM_001195799.2:c.1318G>A
NM_001195800.2:c.937G>A
NM_001195803.2:c.1060G>A
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Uncertain Significance

Met criteria codes 2
PP3 PM2
Not Met criteria codes 5
BP4 PS1 PM5 BA1 BS1

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.1441G>A (p.Val481Met) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on February 28, 2025. The supporting evidence is as follows: PM2: PopMax MAF = 0.0000008475 (0.00008475%) in European (non-Finnish) exomes + genomes (gnomAD v4.1.0). PP3: REVEL = 0.83.
Met criteria codes
PP3
REVEL = 0.83, It is above 0.75
PM2
PopMax MAF = 0.0000008475 (0.00008475%) in European (non-Finnish) exomes (gnomAD v4.1.0)
Not Met criteria codes
BP4
REVEL = 0.83, It is not below 0.50
PS1
There are no other missense variants in the same codon
PM5
There are no other missense variants in the same codon
BA1
Variant is absent in gnomAD v4.1.0
BS1
Variant is absent in gnomAD v4.1.0
Curation History
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