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]
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  • 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.188G>T (p.Cys63Phe)

CA404075130

440548 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 15c6af1a-1f39-4487-8fc0-8c247feec6bc
Approved on: 2023-03-27
Published on: 2024-10-04

HGVS expressions

NM_000527.5:c.188G>T
NM_000527.5(LDLR):c.188G>T (p.Cys63Phe)
NC_000019.10:g.11100343G>T
CM000681.2:g.11100343G>T
NC_000019.9:g.11211019G>T
CM000681.1:g.11211019G>T
NC_000019.8:g.11072019G>T
NG_009060.1:g.15963G>T
ENST00000252444.10:c.446G>T
ENST00000559340.2:c.188G>T
ENST00000560467.2:c.188G>T
ENST00000558518.6:c.188G>T
ENST00000252444.9:c.442G>T
ENST00000455727.6:c.188G>T
ENST00000535915.5:c.188G>T
ENST00000545707.5:c.188G>T
ENST00000557933.5:c.188G>T
ENST00000557958.1:n.274G>T
ENST00000558013.5:c.188G>T
ENST00000558518.5:c.188G>T
ENST00000560502.5:n.274G>T
NM_000527.4:c.188G>T
NM_001195798.1:c.188G>T
NM_001195799.1:c.188G>T
NM_001195800.1:c.188G>T
NM_001195803.1:c.188G>T
NM_001195798.2:c.188G>T
NM_001195799.2:c.188G>T
NM_001195800.2:c.188G>T
NM_001195803.2:c.188G>T

Uncertain Significance

Met criteria codes 3
PP3 PM1 PM2
Not Met criteria codes 23
BA1 PS2 PS4 PS3 PS1 PP1 PP4 PP2 PM3 PM5 PM4 PM6 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP3 BP4 BP1 PVS1

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.188G>T (p.Cys63Phe) 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 27 March 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL = 0.921. PM1: Variant is missense, meets PM2, and alters Cys63, one of the 60 highly conserved cysteine residues.
Met criteria codes
PP3
REVEL = 0.921. It is above 0.75.
PM1
Variant is missense, meets PM2 and alters Cys63, one of the 60 highly conserved cysteine residues
PM2
This variant is absent from gnomAD (gnomAD v2.1.1)
Not Met criteria codes
BA1
This variant is absent from gnomAD (gnomAD v2.1.1)
PS2
No de novo cases were identified
PS4
variant meets PM2, but there is no record of being identified in index cases with clinical criteria for FH
PS3
No functional assays performed/found
PS1
Variant meets PM1 - not applicable.
PP1
no family members tested
PP4
variant meets PM2, but there is no record of being identified in index cases with clinical criteria for FH
PP2
not applicable
PM3
variant not identified in index cases with more than 1 variant
PM5
Variant meets PM1 - not applicable.
PM4
Missense variant - not applicable
PM6
No de novo cases were identified
BS2
Variant not identified in normolipidemic individuals
BS4
no family members tested
BS3
No functional assays performed/found
BS1
This variant is absent from gnomAD (gnomAD v2.1.1)
BP5
not applicable
BP7
Missense variant - not applicable
BP2
variant not identified in index cases with more than 1 variant
BP3
not applicable
BP4
REVEL = 0.921. Score is not below 0.50
BP1
not applicable
PVS1
Missense variant - not applicable
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