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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • cspecId property did not resolve into a valid CSPEC request: https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/135640393!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000527.5(LDLR):c.642G>A (p.Trp214Ter)

CA10585029

251340 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: ecdf9c5f-f262-4f76-aee8-d7a7e435de78
Approved on: 2021-12-13
Published on: 2022-01-01

HGVS expressions

NM_000527.5:c.642G>A
NM_000527.5(LDLR):c.642G>A (p.Trp214Ter)
NC_000019.10:g.11105548G>A
CM000681.2:g.11105548G>A
NC_000019.9:g.11216224G>A
CM000681.1:g.11216224G>A
NC_000019.8:g.11077224G>A
NG_009060.1:g.21168G>A
ENST00000252444.10:c.900G>A
ENST00000559340.2:c.642G>A
ENST00000560467.2:c.642G>A
ENST00000558518.6:c.642G>A
ENST00000252444.9:c.896G>A
ENST00000455727.6:c.314-1844G>A
ENST00000535915.5:c.519G>A
ENST00000545707.5:c.314-1017G>A
ENST00000557933.5:c.642G>A
ENST00000558013.5:c.642G>A
ENST00000558518.5:c.642G>A
ENST00000560467.1:c.242G>A
NM_000527.4:c.642G>A
NM_001195798.1:c.642G>A
NM_001195799.1:c.519G>A
NM_001195800.1:c.314-1844G>A
NM_001195803.1:c.314-1017G>A
NM_001195798.2:c.642G>A
NM_001195799.2:c.519G>A
NM_001195800.2:c.314-1844G>A
NM_001195803.2:c.314-1017G>A
More

Pathogenic

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

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.642G>A (p.Trp214Ter) 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/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PVS1 - variant is nonsense in exon 4 (amino terminal of amino acid 830), so PVS1 is met. PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is met. PP4 - variant meets PM2 and was identified in at least 1 index case with SB criteria of definite FH (A+B) (Diagnostic criteria for heterozygous FH used in the paper were a TC>8.0 mmol/l and LDL- C>6.0 mmol/l if available, tendon xanthomata in the patient or in a first-degree relative, and a family history of hypercholesterolemia) from PMID 10532689 (Jensen et al., 1999), Denmark. so PP4 is met.
Met criteria codes
PVS1
variant is nonsense in exon 4 (amino terminal of amino acid 830), so PVS1 is met
PP4
variant meets PM2 and was identified in: - at least 1 index case with SB criteria of definite FH (A+B) (Diagnostic criteria for heterozygous FH used in the paper were a TC>8.0 mmol/l and LDL- C>6.0 mmol/l if available, tendon xanthomata in the patient or in a first-degree relative, and a family history of hypercholesterolemia) from PMID 10532689 (Jensen et al., 1999), Denmark. so PP4 is met
PM2
This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is met
Not Met criteria codes
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS4
no segregation data
BS3
variant was not studied in functional study
BS2
variant was not searched in normolipidemic individuals
BP5
not applicable
BP7
variant is nonsense, so not applicable
BP4
variant meets PVS1, so not met
BP3
not applicable
BP1
not applicable
BP2
no other variants identified in index cases
PS1
variant is nonsense, so not applicable
PS2
no de novo occurrence identified
PS3
variant was not studied in functional study
PS4
variant meets PM2 and was identified in: - at least 1 index case with SB criteria of definite FH (A+B) (Diagnostic criteria for heterozygous FH used in the paper were a TC>8.0 mmol/l and LDL- C>6.0 mmol/l if available, tendon xanthomata in the patient or in a first-degree relative, and a family history of hypercholesterolemia) from PMID 10532689 (Jensen et al., 1999), Denmark. not enough for PS4, so not met
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PP1
no segregation data
PP2
not applicable
PP3
variant meets PVS1, so not met
PM6
no de novo occurrence identified
PM1
variant is nonsense, so not applicable
PM3
no other variants identified in index cases
PM5
variant is nonsense, so not applicable
PM4
variant is nonsense, so not applicable
Curation History
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