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.1199_1207del (p.Tyr400_Phe402del)

CA10585351

251727 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 77439a5e-7345-4771-8826-a2b0da5d2645
Approved on: 2023-03-20
Published on: 2023-03-31

HGVS expressions

NM_000527.5:c.1199_1207del
NM_000527.5(LDLR):c.1199_1207del (p.Tyr400_Phe402del)
NC_000019.10:g.11113290_11113298del
CM000681.2:g.11113290_11113298del
NC_000019.9:g.11223966_11223974del
CM000681.1:g.11223966_11223974del
NC_000019.8:g.11084966_11084974del
NG_009060.1:g.28910_28918del
ENST00000558518.6:c.1199_1207del
ENST00000252444.9:n.1453_1461del
ENST00000455727.6:c.695_703del
ENST00000535915.5:c.1076_1084del
ENST00000545707.5:c.818_826del
ENST00000557933.5:c.1199_1207del
ENST00000558013.5:c.1199_1207del
ENST00000558518.5:c.1199_1207del
ENST00000560173.1:n.198_206del
ENST00000560467.1:n.679_687del
NM_000527.4:c.1199_1207del
NM_001195798.1:c.1199_1207del
NM_001195799.1:c.1076_1084del
NM_001195800.1:c.695_703del
NM_001195803.1:c.818_826del
NM_001195798.2:c.1199_1207del
NM_001195799.2:c.1076_1084del
NM_001195800.2:c.695_703del
NM_001195803.2:c.818_826del
More

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 4
PS4 PP4 PM2 PM4
Not Met criteria codes 18
PVS1 PS2 PS3 PS1 BA1 PP1 PP3 PM6 PM3 PM1 PM5 BS2 BS4 BS3 BS1 BP2 BP3 BP4

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.1199_1207del (p.Tyr400_Phe402del) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PS4, PM2, PM4, and PP4 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: PS4: Variant meets PM2 and is identified in 19 unrelated FH index cases (18 with DLCN criteria>=6 from PMID: 18243212 (Alonso et al., 2008), and 1 with DLCN criteria from PMID 27784735 (Sánchez-Hernández et al.,2016)). So PS4 is met. PM2: This variant is absent from gnomAD (gnomAD v2.1.1). So PM2 is met. PM4: Variant meets PM2 and is in frame deletion. So PM4 is met. PP4: Variant meets PM2 and is identified in 19 unrelated index cases who fulfill clinical criteria for FH (see PS4 for details). So PP4 is met.
Met criteria codes
PS4
Variant meets PM2 and is identified in 19 unrelated FH index cases (18 with DLCN criteria>=6 from PMID: 18243212 (Alonso et al., 2008), and 1 with DLCN criteria from PMID 27784735 (Sánchez-Hernández et al.,2016)). So PS4 is met.
PP4
Variant meets PM2 and is identified in 19 unrelated index cases who fulfill clinical criteria for FH (see PS4 for details). So PP4 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1). So PM2 is met.
PM4
Variant meets PM2 and is in frame deletion. So PM4 is met.
Not Met criteria codes
PVS1
Not nonsense, frameshift, canonical +/- 1 or 2 splice sites, initiation codon, single or multiexon deletion
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No data available
PS1
It is not a missense variant.
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PP1
No data available.
PP3
It is not a missense variant.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No data available.
PM1
Not a missense variant
PM5
It is not a missense variant.
BS2
No data available
BS4
No data available.
BS3
No data available
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BP2
No data available.
BP3
in-frame deletion in a non-repeat region
BP4
It is not a missense variant.
Curation History
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