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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000527.5(LDLR):c.1739C>G (p.Ser580Cys)

CA404089700

921461 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 74dfa261-db0e-4b80-bfff-28e2cfbdc80f

Approved on: 2023-11-07

Published on: 2024-09-25

HGVS expressions

NM_000527.5:c.1739C>G

NM_000527.5(LDLR):c.1739C>G (p.Ser580Cys)

NC_000019.10:g.11116892C>G

CM000681.2:g.11116892C>G

NC_000019.9:g.11227568C>G

CM000681.1:g.11227568C>G

NC_000019.8:g.11088568C>G

NG_009060.1:g.32512C>G

ENST00000252444.10:c.1997C>G

ENST00000559340.2:c.1705+680C>G

ENST00000560467.2:c.1619C>G

ENST00000558518.6:c.1739C>G

ENST00000252444.9:c.1993C>G

ENST00000455727.6:c.1235C>G

ENST00000535915.5:c.1616C>G

ENST00000545707.5:c.1358C>G

ENST00000557933.5:c.1739C>G

ENST00000558013.5:c.1739C>G

ENST00000558518.5:c.1739C>G

ENST00000559340.1:c.426+680C>G

NM_000527.4:c.1739C>G

NM_001195798.1:c.1739C>G

NM_001195799.1:c.1616C>G

NM_001195800.1:c.1235C>G

NM_001195803.1:c.1358C>G

NM_001195798.2:c.1739C>G

NM_001195799.2:c.1616C>G

NM_001195800.2:c.1235C>G

NM_001195803.2:c.1358C>G

Uncertain Significance

PP3 PM2

BS2 BS4 BS3 BS1 BP2 BP3 BP4 PS2 PS4 PS3 PS1 PP4 PP1 PVS1 PM6 PM3 PM1 PM4 PM5 BA1

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.1739C>G (p.Ser580Cys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2 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: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.88.

PP3

REVEL=0.88. It is above 0.75, so PP3 is met.

PM2

This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met.

BS2

No data available

BS4

No data available

BS3

No data available

BS1

This variant is absent from gnomAD (gnomAD v2.1.1).

BP2

No data available

BP3

No in-frame deletions/insertions

BP4

REVEL=0.88. It is above 0.5

PS2

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

PS4

No data available

PS3

No data available

PS1

No other missense variant with the same amino acid change

PP4

No data available

PP1

No data available

PVS1

Not a null variant

PM6

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

PM3

No data available

PM1

Not in exon 4, not a cysteine residue.

PM4

No in-frame deletions/insertions

PM5

2 other missense variants in the same codon: - NM_000527.5(LDLR):c.1739C>T (p.Ser580Phe) (ClinVar ID 438325) - Likely pathogenic by these guidelines - NM_000527.5(LDLR):c.1738T>C (p.Ser580Pro) (ClinVar ID 375822) - Uncertain significance by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines.

BA1

This variant is absent from gnomAD (gnomAD v2.1.1).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.