Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.1069G>C (p.Glu357Gln)

CA404083133

431519 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 15637e16-9961-49f0-a23f-20e852660c60
Approved on: 2023-04-28
Published on: 2023-04-30

HGVS expressions

NM_000527.5:c.1069G>C
NM_000527.5(LDLR):c.1069G>C (p.Glu357Gln)
NC_000019.10:g.11111522G>C
CM000681.2:g.11111522G>C
NC_000019.9:g.11222198G>C
CM000681.1:g.11222198G>C
NC_000019.8:g.11083198G>C
NG_009060.1:g.27142G>C
ENST00000558518.6:c.1069G>C
ENST00000252444.9:n.1323G>C
ENST00000455727.6:c.565G>C
ENST00000535915.5:c.946G>C
ENST00000545707.5:c.688G>C
ENST00000557933.5:c.1069G>C
ENST00000558013.5:c.1069G>C
ENST00000558518.5:c.1069G>C
ENST00000560173.1:n.68G>C
ENST00000560467.1:n.549G>C
NM_000527.4:c.1069G>C
NM_001195798.1:c.1069G>C
NM_001195799.1:c.946G>C
NM_001195800.1:c.565G>C
NM_001195803.1:c.688G>C
NM_001195798.2:c.1069G>C
NM_001195799.2:c.946G>C
NM_001195800.2:c.565G>C
NM_001195803.2:c.688G>C
More

Uncertain Significance

Met criteria codes 2
PP3 PM2
Not Met criteria codes 24
PP4 PP1 PP2 PM3 PM1 PM4 PM5 PM6 PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7 PS2 PS4 PS3 PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Familial Hypercholesterolemia Expert Panel Specifications to the ACMG/AMP Variant Classification Guidelines Version 1.2

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.1069G>C (p.Glu357Gln) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2 and 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 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.935.
Met criteria codes
PP3
REVEL = 0.935
PM2
This variant is absent from gnomAD (gnomAD v2.1.1).
Not Met criteria codes
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 other missense variants in the same codon: - NM_000527.5(LDLR):c.1069G>A (p.Glu357Lys) (ClinVar ID 251649) - Likely pathogenic by these guidelines - NM_000527.5(LDLR):c.1070A>G (p.Glu357Gly) (ClinVar ID 251651) - Uncertain significance by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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