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.1189T>C (p.Ser397Pro)

CA404084655

923326 (ClinVar)

Gene: LDLR (HGNC:3949)

Condition: hypercholesterolemia, familial (MONDO:0007750)

Inheritance Mode: Semidominant inheritance

UUID: fcdc1140-e906-4094-ae0a-feca9047e230

Approved on: 2023-06-23

Published on: 2025-09-16

HGVS expressions

NM_000527.5(LDLR):c.1189T>C (p.Ser397Pro)

NM_000527.5:c.1189T>C

NC_000019.10:g.11113280T>C

CM000681.2:g.11113280T>C

NC_000019.9:g.11223956T>C

CM000681.1:g.11223956T>C

NC_000019.8:g.11084956T>C

NG_009060.1:g.28900T>C

ENST00000252444.10:c.1447T>C

ENST00000559340.2:c.1189T>C

ENST00000560467.2:c.1069T>C

ENST00000558518.6:c.1189T>C

ENST00000252444.9:c.1443T>C

ENST00000455727.6:c.685T>C

ENST00000535915.5:c.1066T>C

ENST00000545707.5:c.808T>C

ENST00000557933.5:c.1189T>C

ENST00000558013.5:c.1189T>C

ENST00000558518.5:c.1189T>C

ENST00000560173.1:n.188T>C

ENST00000560467.1:c.669T>C

NM_000527.4:c.1189T>C

NM_001195798.1:c.1189T>C

NM_001195799.1:c.1066T>C

NM_001195800.1:c.685T>C

NM_001195803.1:c.808T>C

NM_001195798.2:c.1189T>C

NM_001195799.2:c.1066T>C

NM_001195800.2:c.685T>C

NM_001195803.2:c.808T>C

Uncertain Significance

PM2

BA1 BP4 BS1 PP3 PM5 PS1

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.1189T>C (p.Ser397Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 June 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v20210610).

PM2

This variant is absent from gnomAD (gnomAD v20210610).

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BP4

REVEL = 0.502, it is not below 0.50.

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

REVEL = 0.502, it is not above 0.75, splicing evaluation required. Functional data on splicing not available. A) Variant within limits MES scores: canonical site variant = 7.47; canonical acceptor wt = 6.59. Ratio: 7.47/6.59 = 1.13---- It is not <0.8. Variant is not predicted to alter splicing

PM5

2 other missense variants in the same codon: - NM_000527.5(LDLR):c.1189T>A (p.Ser397Thr) (ClinVar ID 251725) - Uncertain significance by these guidelines - NM_000527.5(LDLR):c.1190C>T (p.Ser397Phe) (ClinVar ID 925475) - Uncertain significance by these guidelines There are no variants in the same codon classified as Pathogenic by these guidelines.

PS1

There are no variants causing the same amino acid change classified as Pathogenic by these guidelines.

Curation History

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