Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.1555C>A (p.Pro519Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10576309

226360 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: f1deffc4-b099-42b7-aa27-9d5d19edae51

Approved on: 2025-03-04

Published on: 2025-03-04

HGVS expressions

NM_000527.5:c.1555C>A

NM_000527.5(LDLR):c.1555C>A (p.Pro519Thr)

NC_000019.10:g.11113731C>A

CM000681.2:g.11113731C>A

NC_000019.9:g.11224407C>A

CM000681.1:g.11224407C>A

NC_000019.8:g.11085407C>A

NG_009060.1:g.29351C>A

ENST00000252444.10:c.1813C>A

ENST00000559340.2:c.1555C>A

ENST00000560467.2:c.1435C>A

ENST00000558518.6:c.1555C>A

ENST00000252444.9:c.1809C>A

ENST00000455727.6:c.1051C>A

ENST00000535915.5:c.1432C>A

ENST00000545707.5:c.1174C>A

ENST00000557933.5:c.1555C>A

ENST00000558013.5:c.1555C>A

ENST00000558518.5:c.1555C>A

ENST00000559340.1:c.276C>A

NM_000527.4:c.1555C>A

NM_001195798.1:c.1555C>A

NM_001195799.1:c.1432C>A

NM_001195800.1:c.1051C>A

NM_001195803.1:c.1174C>A

NM_001195798.2:c.1555C>A

NM_001195799.2:c.1432C>A

NM_001195800.2:c.1051C>A

NM_001195803.2:c.1174C>A

Uncertain Significance

PP4 PP3 PM2

PM5

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

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>A (p.Pro519Thr) 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 (specification version 1.2) on 4 March 2025. The supporting evidence is as follows: PM2: This variant is absent from a distinct subpopulation in gnomAD v4.1.0 and is found in 1/62500 alleles in the Remaining subpopulation. PP3: REVEL = 0.778. PP4: Variant meets PM2 and is identified in at least 1 index case with DLCN score >=6 after alternative causes of high cholesterol were excluded (Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA, Australia).

PP4

Variant meets PM2 and is identified in at least 1 index case who fulfills DLCN>=6 criteria for FH after alternative causes of high cholesterol were excluded (Cardiovascular Genetics Laboratory ,PathWest Laboratory Medicine WA)

PP3

REVEL = 0.778.

PM2

This variant is absent from a distinct subpopulation in gnomAD v4.1.0 and is found in 1/62500 alleles in the Remaining subpopulation.

PM5

NM_000527.5(LDLR):c.1555C>T (p.Pro519Ser) is classified as VUS by VCEP guidelines.

Curation History

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