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.1571T>G (p.Val524Gly)

CA10585506

251901 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 12e5d4fd-7bac-43b7-9718-f95a32f4757d
Approved on: 2025-03-24
Published on: 2025-03-24

HGVS expressions

NM_000527.5:c.1571T>G
NM_000527.5(LDLR):c.1571T>G (p.Val524Gly)
NC_000019.10:g.11113747T>G
CM000681.2:g.11113747T>G
NC_000019.9:g.11224423T>G
CM000681.1:g.11224423T>G
NC_000019.8:g.11085423T>G
NG_009060.1:g.29367T>G
ENST00000252444.10:c.1829T>G
ENST00000559340.2:c.1571T>G
ENST00000560467.2:c.1451T>G
ENST00000558518.6:c.1571T>G
ENST00000252444.9:c.1825T>G
ENST00000455727.6:c.1067T>G
ENST00000535915.5:c.1448T>G
ENST00000545707.5:c.1190T>G
ENST00000557933.5:c.1571T>G
ENST00000558013.5:c.1571T>G
ENST00000558518.5:c.1571T>G
ENST00000559340.1:c.292T>G
NM_000527.4:c.1571T>G
NM_001195798.1:c.1571T>G
NM_001195799.1:c.1448T>G
NM_001195800.1:c.1067T>G
NM_001195803.1:c.1190T>G
NM_001195798.2:c.1571T>G
NM_001195799.2:c.1448T>G
NM_001195800.2:c.1067T>G
NM_001195803.2:c.1190T>G
More

Uncertain Significance

Met criteria codes 3
PP4 PP3 PM2
Not Met criteria codes 18
PP1 PP2 PM1 PM4 BS4 BS3 BS1 BS2 BP7 BP5 BP3 BP4 BP1 PS1 PS4 PS3 BA1 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.1571T>G (p.Val524Gly) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 24 March 2025. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v4.1.0). PP3: REVEL = 0.992. PP4: Variant meets PM2 and is identified in 1 case fulfilling Simon Broome criteria for FH in PMID 17142622 (Humphries et al., 2006), UK.
Met criteria codes
PP4
Variant meets PM2 and is identified in 1 case fulfilling Simon Broome criteria for FH in PMID 17142622 (Humphries et al., 2006), UK.
PP3
REVEL = 0.992. It is above 0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v4.1).
Not Met criteria codes
PP1
not met, (no information of index cases or report of segregation data/cases).
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
not met, (no information of index cases or report of segregation data/cases).
BS3
not met (no information or reports of functional data).
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
not met, (no information of index cases or report of segregation data/cases).
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
not met, (no information of index cases or report of segregation data/cases).
PS3
not met (no information or reports of functional data).
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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