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]

Variant: NM_000527.5(LDLR):c.915G>T (p.Trp305Cys)

CA404081046

1437514 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: b747ab8a-2b1a-45b9-a12b-360dd1dc8c9a
Approved on: 2023-04-28
Published on: 2023-04-30

HGVS expressions

NM_000527.5:c.915G>T
NM_000527.5(LDLR):c.915G>T (p.Trp305Cys)
NC_000019.10:g.11107489G>T
CM000681.2:g.11107489G>T
NC_000019.9:g.11218165G>T
CM000681.1:g.11218165G>T
NC_000019.8:g.11079165G>T
NG_009060.1:g.23109G>T
ENST00000558518.6:c.915G>T
ENST00000252444.9:n.1169G>T
ENST00000455727.6:c.411G>T
ENST00000535915.5:c.792G>T
ENST00000545707.5:c.534G>T
ENST00000557933.5:c.915G>T
ENST00000558013.5:c.915G>T
ENST00000558518.5:c.915G>T
ENST00000558528.1:n.430G>T
ENST00000560467.1:n.515G>T
NM_000527.4:c.915G>T
NM_001195798.1:c.915G>T
NM_001195799.1:c.792G>T
NM_001195800.1:c.411G>T
NM_001195803.1:c.534G>T
NM_001195798.2:c.915G>T
NM_001195799.2:c.792G>T
NM_001195800.2:c.411G>T
NM_001195803.2:c.534G>T
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Uncertain Significance

Met criteria codes 2
PP3 PM2
Not Met criteria codes 20
PVS1 BA1 BS4 BS3 BS1 BS2 BP2 BP3 BP4 PS2 PS4 PS3 PS1 PP4 PP1 PM6 PM3 PM1 PM4 PM5

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Familial Hypercholesterolemia VCEP
The NM_000527.5(LDLR):c.915G>T (p.Trp305Cys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2 and PP3 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: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met. PP3: REVEL=0.91. It is above 0.75, so PP3 is met.
Met criteria codes
PP3
REVEL=0.91. It is above 0.75, so PP3 is met.
PM2
This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met.
Not Met criteria codes
PVS1
Not a null variant
BA1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS4
No data available
BS3
No functional studies available.
BS1
This variant is absent from gnomAD (gnomAD v2.1.1).
BS2
No data available.
BP2
No data available
BP3
No in-frame deletions/insertions
BP4
REVEL=0.91. It is above 0.5.
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No data available
PS3
No functional studies available.
PS1
One more missense variant that leads to the same amino acid change: NM_000527.5(LDLR):c.915G>C (p.Trp305Cys) (ClinVar ID 251521) Uncertain significance by these guidelines.
PP4
No data available
PP1
No data available
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No data available
PM1
Not on exon 4. Not a cysteine residue.
PM4
No in-frame deletions/insertions
PM5
1 other missense variant in the same codon: NM_000527.5(LDLR):c.914G>C (p.Trp305Ser) (ClinVar ID 251519) Uncertain significance by these guidelines. There is no variant in the same codon classified as Pathogenic by these guidelines.
Curation History
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