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

Variant: NM_000527.5(LDLR):c.1555C>T (p.Pro519Ser)

CA10585501

251896 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 696527eb-a40e-4563-a1a5-37278db5796e
Approved on: 2025-03-04
Published on: 2025-03-04

HGVS expressions

NM_000527.5:c.1555C>T
NM_000527.5(LDLR):c.1555C>T (p.Pro519Ser)
NC_000019.10:g.11113731C>T
CM000681.2:g.11113731C>T
NC_000019.9:g.11224407C>T
CM000681.1:g.11224407C>T
NC_000019.8:g.11085407C>T
NG_009060.1:g.29351C>T
ENST00000252444.10:c.1813C>T
ENST00000559340.2:c.1555C>T
ENST00000560467.2:c.1435C>T
ENST00000558518.6:c.1555C>T
ENST00000252444.9:c.1809C>T
ENST00000455727.6:c.1051C>T
ENST00000535915.5:c.1432C>T
ENST00000545707.5:c.1174C>T
ENST00000557933.5:c.1555C>T
ENST00000558013.5:c.1555C>T
ENST00000558518.5:c.1555C>T
ENST00000559340.1:c.276C>T
NM_000527.4:c.1555C>T
NM_001195798.1:c.1555C>T
NM_001195799.1:c.1432C>T
NM_001195800.1:c.1051C>T
NM_001195803.1:c.1174C>T
NM_001195798.2:c.1555C>T
NM_001195799.2:c.1432C>T
NM_001195800.2:c.1051C>T
NM_001195803.2:c.1174C>T
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Uncertain Significance

Met criteria codes 4
PS4_Supporting PP4 PP3 PM2
Not Met criteria codes 1
PM5

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.1555C>T (p.Pro519Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3, PP4 and PS4_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 4 March 2025. The supporting evidence is as follows: PM2: This variant is absent from gnomAD v4.1.0. PP3: REVEL = 0.864. PS4_Supporting, PP4: Variant meets PM2 and is identified in at least 3 unrelated index cases who fulfill criteria for FH from different labs (1 case with possible FH by Simon Broome criteria from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), France; 2 cases with definite FH by Simon Broome criteria from PMID 35047021 (Rimbert et al., 2022)).
Met criteria codes
PS4_Supporting
Variant meets PM2 and is identified in at least 3 unrelated index cases who fulfill SB possible/definite or DLCN>=6 criteria for FH from different labs. (1) Variant meets PM2 and is identified in 1 FH patient meeting SB possible FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière) (2) Variant meets PM2 and is identified in 2 unrelated FH patients meeting SB definite FH from PMID: 35047021
PP4
Variant meets PM2 and is identified in at least 1 index case who fulfills SB possible FH criteria after alternative causes of high cholesterol were excluded (Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière)
PP3
REVEL = 0.864.
PM2
This variant is absent from gnomAD v4.1.0.
Not Met criteria codes
PM5
NM_000527.5(LDLR):c.1555C>A (p.Pro519Thr) variant is classified as VUS by VCEP guidelines.
Curation History
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