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.1749C>G (p.His583Gln)

CA404089716

441220 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 8625c1db-5d72-4fd0-baab-8f9639bc9984
Approved on: 2023-11-07
Published on: 2024-12-24

HGVS expressions

NM_000527.5:c.1749C>G
NM_000527.5(LDLR):c.1749C>G (p.His583Gln)
NC_000019.10:g.11116902C>G
CM000681.2:g.11116902C>G
NC_000019.9:g.11227578C>G
CM000681.1:g.11227578C>G
NC_000019.8:g.11088578C>G
NG_009060.1:g.32522C>G
ENST00000252444.10:c.2007C>G
ENST00000559340.2:c.1705+690C>G
ENST00000560467.2:c.1629C>G
ENST00000558518.6:c.1749C>G
ENST00000252444.9:c.2003C>G
ENST00000455727.6:c.1245C>G
ENST00000535915.5:c.1626C>G
ENST00000545707.5:c.1368C>G
ENST00000557933.5:c.1749C>G
ENST00000558013.5:c.1749C>G
ENST00000558518.5:c.1749C>G
ENST00000559340.1:c.426+690C>G
NM_000527.4:c.1749C>G
NM_001195798.1:c.1749C>G
NM_001195799.1:c.1626C>G
NM_001195800.1:c.1245C>G
NM_001195803.1:c.1368C>G
NM_001195798.2:c.1749C>G
NM_001195799.2:c.1626C>G
NM_001195800.2:c.1245C>G
NM_001195803.2:c.1368C>G
More

Uncertain Significance

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

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
NM_000527.5(LDLR):c.1749C>G (p.His583Gln) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM5 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 7 November 2023. The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL = 0.805. PM5: There is 1 variant in the same codon classified as Pathogenic by these guidelines, NM_000527.5(LDLR):c.1747C>T (p.His583Tyr) (ClinVar ID: 200921).
Met criteria codes
PP3
REVEL = 0.805. It is above 0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1).
PM5
NM_000527.5(LDLR):c.1747C>T (p.His583Tyr) (ClinVar ID: 200921) considered as pathogenic by these guidelines.
Not Met criteria codes
PP4
not met, (no information of index cases or report of segregation data/cases).
PP1
not met, (no information of index cases or report of segregation data/cases).
PP2
N/A according to FHVCEP guidelines
PM6
No de novo occurrence
PS2
No de novo occurrence
PS4
not met, (no information of index cases or report of segregation data/cases).
PS1
Another variant gives the same amino acid change, NM_000527.5(LDLR):c.1749C>A (p.His583Gln) (ClinVar ID: 252014) but is only classified as likely pathogenic by these guidelines.
PS3
not met (no information or reports of functional data).
PM3
Not identified in index cases with more than 1 variant
PM4
Missense variant - LDLR gene, exon 12
PM1
Variant in exon 12 of the LDLR gene (not located at exon 4)
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
PVS1
Missense variant - LDLR gene, exon 12
BP7
Missense variant - LDLR gene, exon 12
BP5
N/A according to FHVCEP guidelines
BP2
Not identified in index cases with more than 1 variant
BP3
Missense variant - LDLR gene, exon 12
BP4
REVEL = 0.805. It is not bellow 0.5, so BP4 is not met.
BP1
N/A according to FHVCEP guidelines
BS4
not met, (no information of index cases or report of segregation data/cases).
BS3
not met (no information or reports of functional data).
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS2
not met, (no information of index cases or report of segregation data/cases).
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.