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]

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Variant: NM_000527.5(LDLR):c.1156G>T (p.Asp386Tyr)

CA404083811

440627 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 0fdbc777-aba1-4c7e-b300-32053f2a5828

HGVS expressions

NM_000527.5:c.1156G>T

NM_000527.5(LDLR):c.1156G>T (p.Asp386Tyr)

NC_000019.10:g.11111609G>T

CM000681.2:g.11111609G>T

NC_000019.9:g.11222285G>T

CM000681.1:g.11222285G>T

NC_000019.8:g.11083285G>T

NG_009060.1:g.27229G>T

ENST00000558518.6:c.1156G>T

ENST00000252444.9:n.1410G>T

ENST00000455727.6:c.652G>T

ENST00000535915.5:c.1033G>T

ENST00000545707.5:c.775G>T

ENST00000557933.5:c.1156G>T

ENST00000558013.5:c.1156G>T

ENST00000558518.5:c.1156G>T

ENST00000560173.1:n.155G>T

ENST00000560467.1:n.636G>T

NM_000527.4:c.1156G>T

NM_001195798.1:c.1156G>T

NM_001195799.1:c.1033G>T

NM_001195800.1:c.652G>T

NM_001195803.1:c.775G>T

NM_001195798.2:c.1156G>T

NM_001195799.2:c.1033G>T

NM_001195800.2:c.652G>T

NM_001195803.2:c.775G>T

Uncertain Significance

PP3 PM2

PS3 PM5

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.1156G>T (p.Asp386Tyr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3) 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: PopMax MAF = 0.00001 in European (Non-Finnish) population in gnomAD (gnomAD v2.1.1). PP3: REVEL score = 0.883, it is above the threshold of 0.75.

PP3

REVEL score = 0.883, it is above the threshold of 0.75.

PM2

PopMax MAF = 0.00001 in European (Non-Finnish) population in gnomAD (gnomAD v2.1.1).

PS3

Functional data is not available.

PM5

There is one other variant in the same codon: LDLR: NM_000527:c.1158C>G (p.Asp386Glu) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

Approved on: 2022-03-25

Published on: 2022-04-25

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