Variant: NM_000527.5(LDLR):c.1221C>T (p.His407=)

CA505743141

430774 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 04e95969-168a-4ce5-a889-deeb413333ea

Approved on: 2022-08-29

Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.1221C>T
NM_000527.5(LDLR):c.1221C>T (p.His407=)
NC_000019.10:g.11113312C>T
CM000681.2:g.11113312C>T
NC_000019.9:g.11223988C>T
CM000681.1:g.11223988C>T
NC_000019.8:g.11084988C>T
NG_009060.1:g.28932C>T
ENST00000558518.6:c.1221C>T
ENST00000252444.9:n.1475C>T
ENST00000455727.6:c.717C>T
ENST00000535915.5:c.1098C>T
ENST00000545707.5:c.840C>T
ENST00000557933.5:c.1221C>T
ENST00000558013.5:c.1221C>T
ENST00000558518.5:c.1221C>T
ENST00000560173.1:n.220C>T
ENST00000560467.1:n.701C>T
NM_000527.4:c.1221C>T
NM_001195798.1:c.1221C>T
NM_001195799.1:c.1098C>T
NM_001195800.1:c.717C>T
NM_001195803.1:c.840C>T
NM_001195798.2:c.1221C>T
NM_001195799.2:c.1098C>T
NM_001195800.2:c.717C>T
NM_001195803.2:c.840C>T

Uncertain Significance

• Met criteria codes: BP7 BP4 PM2

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5(LDLR):c.1221C>T (p.His407=) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, BP4, BP7) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). BP4 - No REVEL, splicing evaluation required. Functional data not available A) not on limits B) does not create AG Variant not predicted to alter splicing BP7 - Variant is synonymous and meets BP4.

Met criteria codes

• BP7: BP7 - Variant is synonymous and meets BP4.
• BP4: BP4 - No REVEL, splicing evaluation required. Functional data not available A) not on limits B) does not create AG Variant not predicted to alter splicing
• PM2: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1).