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.1898G>T (p.Arg633Leu)

CA10585677

252107 (ClinVar)

Gene: LDLR (HGNC:3949)
Condition: hypercholesterolemia, familial (MONDO:0007750)
Inheritance Mode: Semidominant inheritance
UUID: 3807abd5-9d1c-4dbb-b1fc-4b4f1cd6837b
Approved on: 2023-11-07
Published on: 2025-08-26

HGVS expressions

NM_000527.5(LDLR):c.1898G>T (p.Arg633Leu)
NM_000527.5:c.1898G>T
NC_000019.10:g.11120144G>T
CM000681.2:g.11120144G>T
NC_000019.9:g.11230820G>T
CM000681.1:g.11230820G>T
NC_000019.8:g.11091820G>T
NG_009060.1:g.35764G>T
ENST00000252444.10:c.2156G>T
ENST00000559340.2:c.1758G>T
ENST00000560467.2:c.1778G>T
ENST00000558518.6:c.1898G>T
ENST00000252444.9:c.2152G>T
ENST00000455727.6:c.1394G>T
ENST00000535915.5:c.1775G>T
ENST00000545707.5:c.1517G>T
ENST00000557933.5:c.1898G>T
ENST00000558013.5:c.1898G>T
ENST00000558518.5:c.1898G>T
ENST00000559340.1:c.479G>T
NM_000527.4:c.1898G>T
NM_001195798.1:c.1898G>T
NM_001195799.1:c.1775G>T
NM_001195800.1:c.1394G>T
NM_001195803.1:c.1517G>T
NM_001195798.2:c.1898G>T
NM_001195799.2:c.1775G>T
NM_001195800.2:c.1394G>T
NM_001195803.2:c.1517G>T
More

Likely Pathogenic

Met criteria codes 4
PP4 PP3 PM2 PM5
Not Met criteria codes 18
PS2 PS4 PS3 PS1 PP1 BA1 PM6 BS4 BS3 BS1 PM3 PM1 PM4 BS2 BP7 BP2 BP4 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.1898G>T (p.Arg633Leu) variant is classified as Likely Pathogenic for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM5, PP4 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 7 November 2023. The supporting evidence is as follows: PM2: Absent from gnomAD version v2.1.1. PP3: REVEL= 0.899. PM5: There is a variant in the same codon classified as Pathogenic by these guidelines, NM_000527.5(LDLR):c.1898G>A (p.Arg633His) (ClinVar ID: 226380). PP4: Variant meets PM2 and is identified in at least 1 index case who fulfills criteria for FH from PMID 16250003 (Fouchier et al., 2005), The Netherlands, after alternative causes of high cholesterol were excluded.
Met criteria codes
PP4
Variant meets PM2 and is identified in at least 1 index case who fulfills definite criteria for FH from PMID 16250003, after alternative causes of high cholesterol were excluded.
PP3
REVEL= 0.899. This is greater than 0.75 so PP3 is met.
PM2
Absent from gnomAD version v 2.1.1
PM5
There is a variant in the same codon classified as Pathogenic by these guidelines, NM_000527.5(LDLR):c.1898G>A (p.Arg633His) (ClinVar ID: 226380).
Not Met criteria codes
PS2
Not met.
PS4
No data available.
PS3
No data available.
PS1
No pathogenic variants at same codon leading to same amino acid change.
PP1
No data available.
BA1
Absent from gnomAD version v 2.1.1
PM6
Not met.
BS4
No data available.
BS3
No data available.
BS1
Absent from gnomAD version v 2.1.1
PM3
No data available.
PM1
Not a missense variant in exon 4 or on a cysteine residue.
PM4
Not an in-frame deletion/insertion.
BS2
No data available.
BP7
Not a synonymous variant.
BP2
No data available.
BP4
REVEL= 0.899. This is greater than 0.5 so BP4 is not met.
PVS1
Not a null variant.
Curation History
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