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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000527.4(LDLR):c.1323C>T (p.Ile441=)

CA033568

456650 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: fba360f5-6b2f-4315-aa0e-fec7b1bab020

HGVS expressions

NM_000527.4:c.1323C>T
NM_000527.4(LDLR):c.1323C>T (p.Ile441=)
ENST00000558518.6:c.1323C>T
ENST00000252444.9:n.1577C>T
ENST00000455727.6:c.819C>T
ENST00000535915.5:c.1200C>T
ENST00000545707.5:c.942C>T
ENST00000557933.5:c.1323C>T
ENST00000558013.5:c.1323C>T
ENST00000558518.5:c.1323C>T
ENST00000559340.1:n.44C>T
ENST00000560173.1:n.322C>T
ENST00000560467.1:n.803C>T
NM_001195798.1:c.1323C>T
NM_001195799.1:c.1200C>T
NM_001195800.1:c.819C>T
NM_001195803.1:c.942C>T
NM_000527.5:c.1323C>T
NM_001195798.2:c.1323C>T
NM_001195799.2:c.1200C>T
NM_001195800.2:c.819C>T
NM_001195803.2:c.942C>T
NC_000019.10:g.11113414C>T
CM000681.2:g.11113414C>T
NC_000019.9:g.11224090C>T
CM000681.1:g.11224090C>T
NC_000019.8:g.11085090C>T
NG_009060.1:g.29034C>T

Benign

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

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.4(LDLR):c.1323C>T (p.Ile441=) variant is classified as Benign for Familial Hypercholesterolemia by applying evidence codes BS1, BS2, BP4 and BP7 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: BS1 - FAF = 0.003722 (0.37%) in African exomes (gnomAD v2.1.1). BS2 - Variant is observed in heterozygosity in 5 normolipidemic adults. BP4 - no REVEL, splicing evaluation required. No functional study performed. A) not on limits B) does not create GT C) no GT nearby. BP7 - Variant is synonymous and meets BP4.
Met criteria codes
BS1
FAF = 0.003722 (0.37%) in African exomes (gnomAD v2.1.1); meets BS1 threshold of >0.2%
BS2
Variant is observed in heterozygosity in 5 normolipidemic adults (Color)
BP4
no REVEL, splicing evaluation required. No functional study performed. A) not on limits B) does not create GT C) no GT nearby BP4 is met
BP7
Variant is synonymous and meets BP4, so BP7 is met
Not Met criteria codes
BS4
No segregation data available
BS3
No functional data available
BP2
Not observed in data available
BP3
NA
BP1
NA
BP5
NA
PS2
No de novo data available
PS4
does not meet PM2 caveat
PS3
No functional data available
PS1
NA; synonymous
BA1
FAF = 0.003722 (0.37%) in African exomes (gnomAD v2.1.1)
PP4
PM2 caveat not met
PP1
No segregation data available
PP3
no REVEL, splicing evaluation required. No functional study performed. A) not on limits B) does not create GT C) no GT nearby PP3 is not met
PP2
NA
PM3
Not observed in data available, PM2 caveat not met
PM1
NA; synonymous
PM4
NA; synonymous
PM5
NA; synonymous
PVS1
NA; synonymous
PM6
No de novo data available
PM2
PopMax MAF = 0.004729 (0.47%) in African exomes (gnomAD v2.1.1)
Approved on: 2021-06-23
Published on: 2021-06-24
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