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.899G>A (p.Arg300Lys)

CA404080996

924646 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 0ee29911-b0c3-4c94-aa5a-d90fa20eece5

HGVS expressions

NM_000527.5:c.899G>A

NM_000527.5(LDLR):c.899G>A (p.Arg300Lys)

NC_000019.10:g.11107473G>A

CM000681.2:g.11107473G>A

NC_000019.9:g.11218149G>A

CM000681.1:g.11218149G>A

NC_000019.8:g.11079149G>A

NG_009060.1:g.23093G>A

ENST00000558518.6:c.899G>A

ENST00000252444.9:n.1153G>A

ENST00000455727.6:c.395G>A

ENST00000535915.5:c.776G>A

ENST00000545707.5:c.518G>A

ENST00000557933.5:c.899G>A

ENST00000558013.5:c.899G>A

ENST00000558518.5:c.899G>A

ENST00000558528.1:n.414G>A

ENST00000560467.1:n.499G>A

NM_000527.4:c.899G>A

NM_001195798.1:c.899G>A

NM_001195799.1:c.776G>A

NM_001195800.1:c.395G>A

NM_001195803.1:c.518G>A

NM_001195798.2:c.899G>A

NM_001195799.2:c.776G>A

NM_001195800.2:c.395G>A

NM_001195803.2:c.518G>A

Uncertain Significance

BP4 PM2

PP3 PM5 PM1

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 variant NM_000527.5(LDLR):c.899G>A (p.Arg300Lys) is classified as a variant of uncertain significance for Familial Hypercholesterolemia by applying evidence codes PM2 and BP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2_Met : This variant is absent from controls in gnomAD (V2.1.1) BP4_Met : REVEL = 0.366. It is below 0.50. Functional data on splicing not available A) Not on limits B) Does not create AG nor GT C) nearby GT Variant is not predicted to alter splicing

BP4

REVEL = 0.366. It is below 0.50. Functional data on splicing not available A) Not on limits B) Does not create AG nor GT C) nearby GT Variant is not predicted to alter splicing

PM2

This variant is absent from controls in gnomAD (V2.1.1)

PP3

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

PM5

There is 1 missense variant in the same codon (c.898A>G (p.Arg300Gly)) not classified as pathogenic by these guidelines

PM1

Variant is not Located in a mutational hot spot and/or critical and well-established functional domain.

Approved on: 2022-10-28

Published on: 2022-12-24

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