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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000527.5(LDLR):c.311G>T (p.Cys104Phe)

CA10584839

251130 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: c11bda52-74fa-4a86-85c5-2790d8ebd5bf
Approved on: 2024-02-23
Published on: 2024-10-07

HGVS expressions

NM_000527.5:c.311G>T
NM_000527.5(LDLR):c.311G>T (p.Cys104Phe)
NC_000019.10:g.11102784G>T
CM000681.2:g.11102784G>T
NC_000019.9:g.11213460G>T
CM000681.1:g.11213460G>T
NC_000019.8:g.11074460G>T
NG_009060.1:g.18404G>T
ENST00000252444.10:c.569G>T
ENST00000559340.2:c.311G>T
ENST00000560467.2:c.311G>T
ENST00000558518.6:c.311G>T
ENST00000252444.9:c.565G>T
ENST00000455727.6:c.311G>T
ENST00000535915.5:c.191-2436G>T
ENST00000545707.5:c.311G>T
ENST00000557933.5:c.311G>T
ENST00000557958.1:n.397G>T
ENST00000558013.5:c.311G>T
ENST00000558518.5:c.311G>T
NM_000527.4:c.311G>T
NM_001195798.1:c.311G>T
NM_001195799.1:c.191-2436G>T
NM_001195800.1:c.311G>T
NM_001195803.1:c.311G>T
NM_001195798.2:c.311G>T
NM_001195799.2:c.191-2436G>T
NM_001195800.2:c.311G>T
NM_001195803.2:c.311G>T
More

Likely Pathogenic

Met criteria codes 4
PP3 PP4 PM1 PM2
Not Met criteria codes 22
PS1 PS2 PS3 PS4 PP1 PP2 BA1 PM3 PM5 PM4 PM6 PVS1 BS1 BS4 BS3 BS2 BP5 BP7 BP4 BP3 BP1 BP2

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.311G>T (p.Cys104Phe) variant is classified as Likely Pathogenic for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM1, PM2, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 February 2024. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v4.0.0). PP3: REVEL = 0.882. PM1: Variant meets PM2 and alters Cys104, one of the cysteine residues listed. PP4: Variant meets PM2 and is identified in at least 1 index case who fulfills clinical criteria for FH from PMID 16159606 (Graham et al., 2005), after alternative causes of high cholesterol were excluded.
Met criteria codes
PP3
PP3 - REVEL = 0.882;
PP4
PP4 - Variant meets PM2 and is identified in at least 1 index case who fulfills clinical criteria for FH (PMID: 16159606), after alternative causes of high cholesterol were excluded
PM1
PM1 - Variant meets PM2 and alters Cys104, one of the cysteine residues listed;
PM2
PM2 - This variant is absent from gnomAD (gnomAD v4.0.0);
Not Met criteria codes
PS1
Not applicable
PS2
No de novo cases were identified
PS3
PS3 - Functional studies are not available.
PS4
PS4 - Variant meets PM2 but was found in only 1 patient with definite FH following Simon Broome criteria (PMID: 16159606).
PP1
no family members tested
PP2
Not applicable
BA1
Not applicable
PM3
Variant meets PM2 but is not identified in an index case with heterozygous or homozygous FH phenotype as well as LDLR variant, in trans, or APOB/PCSK9 variant classified as Pathogenic by these or general ACMG guidelines.
PM5
PM5 - The variant already meets PM1, so PM5 cannot be applied.
PM4
Not applicable
PM6
No de novo cases were identified
PVS1
Not applicable
BS1
Not applicable
BS4
no family members tested
BS3
BS3_Not Met: Functional studies are not available.
BS2
Variant not identified in normolipidemic individuals
BP5
Not applicable
BP7
Not applicable
BP4
REVEL = 0.882. Score is not below 0.50.
BP3
Not applicable
BP1
Not applicable
BP2
Variant meets PM2 but is not identified in an index case with heterozygous or homozygous FH phenotype as well as LDLR variant, in trans, or APOB/PCSK9 variant classified as Pathogenic by these or general ACMG guidelines.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.