Variant: NM_000527.5(LDLR):c.710G>A (p.Arg237His)

CA044568

375798 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 16a530f6-e753-42cb-8dbc-19a74a20358d

Approved on: 2022-04-29

Published on: 2025-02-13

HGVS expressions

NM_000527.5:c.710G>A
NM_000527.5(LDLR):c.710G>A (p.Arg237His)
NC_000019.10:g.11106580G>A
CM000681.2:g.11106580G>A
NC_000019.9:g.11217256G>A
CM000681.1:g.11217256G>A
NC_000019.8:g.11078256G>A
NG_009060.1:g.22200G>A
ENST00000252444.10:c.968G>A
ENST00000559340.2:c.710G>A
ENST00000560467.2:c.710G>A
ENST00000558518.6:c.710G>A
ENST00000252444.9:c.964G>A
ENST00000455727.6:c.314-812G>A
ENST00000535915.5:c.587G>A
ENST00000545707.5:c.329G>A
ENST00000557933.5:c.710G>A
ENST00000558013.5:c.710G>A
ENST00000558518.5:c.710G>A
ENST00000558528.1:n.225G>A
ENST00000560467.1:c.310G>A
NM_000527.4:c.710G>A
NM_001195798.1:c.710G>A
NM_001195799.1:c.587G>A
NM_001195800.1:c.314-812G>A
NM_001195803.1:c.329G>A
NM_001195798.2:c.710G>A
NM_001195799.2:c.587G>A
NM_001195800.2:c.314-812G>A
NM_001195803.2:c.329G>A

Uncertain Significance

• Met criteria codes: PP3 PM2

• Not Met criteria codes: BS3 PS3 PS4 PS1 PP4 PM5

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.710G>A (p.Arg237His) 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 29 April 2022. The supporting evidence is as follows: PM2: PopMax MAF = 0.00008673 (0.009%) in Latino/Admixed American exomes (gnomAD v2.1.1). PP3: REVEL = 0.751. It is above 0.75.

Met criteria codes

• PP3: REVEL = 0.751. It is above 0.75.
• PM2: PopMax MAF = 0.00008673 (0,009%) in atino/Admixed American exomes (gnomAD v2.1.1).

Not Met criteria codes

• BS3: This variant shown to have benign impact in Thormaehlen study (PMID 25647241), but whole cycle is not studied, so not met
• PS3: This variant shown to have benign impact in Thormaehlen study (PMID 25647241)
• PS4: No index case that fulfil FH criteria is reported. So neither PS4 nor PP4 is met.
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No index case that fulfil FH criteria is reported. So neither PS4 nor PP4 is met.
• PM5: There is one other missense variant in the same codon NM_000527.5(LDLR):c.709C>T (p.Arg237Cys). It is considered as Uncertain significance - insufficient evidence by this guidelines. PM5 is not met.