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]
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.5(LDLR):c.718G>T (p.Glu240Ter)

CA10585103

251422 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: ea280cb3-d81a-4dee-a74e-ea4d00773c8a
Approved on: 2021-06-07
Published on: 2021-06-24

HGVS expressions

NM_000527.5:c.718G>T
NM_000527.5(LDLR):c.718G>T (p.Glu240Ter)
ENST00000558518.6:c.718G>T
ENST00000252444.9:n.972G>T
ENST00000455727.6:c.314-804G>T
ENST00000535915.5:c.595G>T
ENST00000545707.5:c.337G>T
ENST00000557933.5:c.718G>T
ENST00000558013.5:c.718G>T
ENST00000558518.5:c.718G>T
ENST00000558528.1:n.233G>T
ENST00000560467.1:n.318G>T
NM_000527.4:c.718G>T
NM_001195798.1:c.718G>T
NM_001195799.1:c.595G>T
NM_001195800.1:c.314-804G>T
NM_001195803.1:c.337G>T
NM_001195798.2:c.718G>T
NM_001195799.2:c.595G>T
NM_001195800.2:c.314-804G>T
NM_001195803.2:c.337G>T
NC_000019.10:g.11106588G>T
CM000681.2:g.11106588G>T
NC_000019.9:g.11217264G>T
CM000681.1:g.11217264G>T
NC_000019.8:g.11078264G>T
NG_009060.1:g.22208G>T
More

Pathogenic

Met criteria codes 3
PP4 PM2 PVS1
Not Met criteria codes 23
PS2 PS4 PS1 PS3 BA1 PP3 PP2 PP1 PM3 PM4 PM1 PM5 PM6 BS2 BS4 BS3 BS1 BP4 BP1 BP2 BP3 BP5 BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.718G>T (p.Glu240Ter) variant is classified as Pathogenic for Familial Hypercholesterolemia by applying evidence codes (PVS1, PM2 and PP4) 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: PVS1 - Variant is nonsense, causing a stop in codon 240. It is upstream of amino acid 830, so PVS1 is Met. PM2 - No population data was found for this variant in gnomAD (gnomAD v2.1.1). PP4 - Variant meets PM2. Variant identified in 1 index case with definite heterozygous hypercholesterolemia by DLCN score from PMID: 16250003.
Met criteria codes
PP4
Variant meets PM2. Variant identified in 1 index case with definite heterozygous hypercholesterolemia by DLCN score from PMID: 16250003.
PM2
No population data was found for this variant in gnomAD (gnomAD v2.1.1).
PVS1
Variant is nonsense, causing a stop in codon 240. It is upstream of amino acid 830, so PVS1 is Met.
Not Met criteria codes
PS2
no de novo cases were identified, so PS2 is Not Met
PS4
Variant meets PM2. Variant identified in 1 index case with definite heterozygous hypercholesterolemia by DLCN score from PMID: 16250003. not enough, so PS4 is Not Met
PS1
Nonsense variant, PS1 not applicable
PS3
no functional assays performed, not applicable
BA1
No population data was found for this variant in gnomAD (gnomAD v2.1.1).
PP3
PVS1 is Met, so PP3 is not applicable
PP2
Not applicable
PP1
no family members were tested, so PP1 is Not Met
PM3
not identified in individuals with other variants, so PM3 is Not Met
PM4
Nonsense variant (PVS1 is Met), PM4 is Not Met
PM1
Nonsense variant, so PM1 is not applicable
PM5
Nonsense variant, PM5 not applicable
PM6
no de novo cases were identified, so PM6 is Not Met
BS2
no unaffected individuals identified with the variant, so BS2 is Not Met
BS4
no family members were tested, so BS4 is Not Met
BS3
no functional assays performed, not applicable
BS1
No population data was found for this variant in gnomAD (gnomAD v2.1.1).
BP4
PVS1 is Met, so BP4 is not applicable
BP1
Not applicable
BP2
not identified in individuals with other variants, so BP2 is Not Met
BP3
Not applicable
BP5
Not applicable
BP7
Nonsense variant, so BP7 is not applicable
Curation History
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