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.1444G>T (p.Asp482Tyr)

CA10585455

251845 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: c4be501c-7d06-4cc7-b16b-790eedd0fe3a
Approved on: 2023-06-23
Published on: 2024-09-25

HGVS expressions

NM_000527.5:c.1444G>T
NM_000527.5(LDLR):c.1444G>T (p.Asp482Tyr)
NC_000019.10:g.11113620G>T
CM000681.2:g.11113620G>T
NC_000019.9:g.11224296G>T
CM000681.1:g.11224296G>T
NC_000019.8:g.11085296G>T
NG_009060.1:g.29240G>T
ENST00000252444.10:c.1702G>T
ENST00000559340.2:c.1444G>T
ENST00000560467.2:c.1324G>T
ENST00000558518.6:c.1444G>T
ENST00000252444.9:c.1698G>T
ENST00000455727.6:c.940G>T
ENST00000535915.5:c.1321G>T
ENST00000545707.5:c.1063G>T
ENST00000557933.5:c.1444G>T
ENST00000558013.5:c.1444G>T
ENST00000558518.5:c.1444G>T
ENST00000559340.1:c.165G>T
ENST00000560467.1:c.924G>T
NM_000527.4:c.1444G>T
NM_001195798.1:c.1444G>T
NM_001195799.1:c.1321G>T
NM_001195800.1:c.940G>T
NM_001195803.1:c.1063G>T
NM_001195798.2:c.1444G>T
NM_001195799.2:c.1321G>T
NM_001195800.2:c.940G>T
NM_001195803.2:c.1063G>T

Uncertain Significance

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

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.1444G>T (p.Asp482Tyr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM5 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 June, 2023. PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.99. PM5: 3 other missense variants in the same codon: - NM_000527.5(LDLR):c.1444G>A (p.Asp482Asn) (ClinVar ID 161284) - Pathogenic by these guidelines; - NM_000527.5(LDLR):c.1444G>C (p.Asp482His) (ClinVar ID 251844) - Likely Pathogenic by these guidelines; - NM_000527.5(LDLR):c.1445A>G (p.Asp482Gly) (ClinVar ID 251846) - Likely Pathogenic by these guidelines; There is 1 variant in the same codon classified as Pathogenic by these guidelines.
Met criteria codes
PP3
REVEL=0.99. It is above 0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met.
PM5
3 other missense variants in the same codon: - NM_000527.5(LDLR):c.1444G>A (p.Asp482Asn) (ClinVar ID 161284) - Pathogenic by these guidelines - NM_000527.5(LDLR):c.1444G>C (p.Asp482His) (ClinVar ID 251844) - Likely Pathogenic by these guidelines - NM_000527.5(LDLR):c.1445A>G (p.Asp482Gly) (ClinVar ID 251846) - Likely Pathogenic by these guidelines There is 1 variant in the same codon classified as Pathogenic by these guidelines. So, PM5 is met.
Not Met criteria codes
PP4
No evidence available.
PP1
No evidence available.
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No evidence available.
PM1
Not in exon 4. Not a cysteine residue.
PM4
No in-frame deletions/insertions
BS2
No evidence available.
BS4
No evidence available.
BS3
No evidence available.
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No evidence available.
PS3
No evidence available.
PS1
No other missense variant in the same codon with the same amino acid change.
BP2
No evidence available.
BP3
No in-frame deletions/insertions
BP4
REVEL=0.99.
PVS1
Not a null variant
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