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]
Link to SEPIO compliant JSON-LD document

Variant: NM_000527.5(LDLR):c.241C>A (p.Arg81Ser)

CA10584803

251088 (ClinVar)

Gene: LDLR
Condition: hypercholesterolemia, familial
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: b0a05e74-6a94-48ff-887d-e2beff2848ba

HGVS expressions

NM_000527.5:c.241C>A
NM_000527.5(LDLR):c.241C>A (p.Arg81Ser)
NC_000019.10:g.11102714C>A
CM000681.2:g.11102714C>A
NC_000019.9:g.11213390C>A
CM000681.1:g.11213390C>A
NC_000019.8:g.11074390C>A
NG_009060.1:g.18334C>A
ENST00000558518.6:c.241C>A
ENST00000252444.9:n.495C>A
ENST00000455727.6:c.241C>A
ENST00000535915.5:c.190+2369C>A
ENST00000545707.5:c.241C>A
ENST00000557933.5:c.241C>A
ENST00000557958.1:n.327C>A
ENST00000558013.5:c.241C>A
ENST00000558518.5:c.241C>A
NM_000527.4:c.241C>A
NM_001195798.1:c.241C>A
NM_001195799.1:c.190+2369C>A
NM_001195800.1:c.241C>A
NM_001195803.1:c.241C>A
NM_001195798.2:c.241C>A
NM_001195799.2:c.190+2369C>A
NM_001195800.2:c.241C>A
NM_001195803.2:c.241C>A

Uncertain Significance

Met criteria codes 2
PP4 PM2
Not Met criteria codes 24
PS2 PS4 PS3 PS1 BP2 BP3 BP4 BP1 BP5 BP7 BA1 PP1 PP3 PP2 PM3 PM1 PM4 PM5 PVS1 PM6 BS2 BS4 BS3 BS1

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.241C>A (p.Arg81Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes 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: PM2 - This variant is absent from gnomAD (v2.1.1). PP4 - Variant meet PM2. PMID: 21382890 (Graaf et al., 2011) - 1 case with LDL-C level >95th percentile for age and gender and autosomal dominant inheritance pattern of hypercholesterolemia, ie, at least 1 biological parent on treatment for hypercholesterolemia and a family history of hypercholesterolemia and cardiovascular disease. Alternative causes of high cholesterol were excluded.
Met criteria codes
PP4
Variant meet PM2. PMID: 21382890 (Graaf et al., 2011) - 1 case with LDL-C level >95th percentile for age and gender and autosomal dominant inheritance pattern of hypercholesterolemia, ie, at least 1 biological parent on treatment for hypercholesterolemia and a family history of hypercholesterolemia and cardiovascular disease. Alternative causes of high cholesterol were excluded.
PM2
This variant is absent from gnomAD (v2.1.1)
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
REVEL = 0.669
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
REVEL = 0.669
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 other missense variants in the same codon: - NM_000527.5(LDLR):c.242G>A (p.Arg81His)(ClinVar ID 924271) - Uncertain significance by these guidelines - NM_000527.5(LDLR):c.241C>T (p.Arg81Cys)(ClinVar ID 183083) - Likely pathogenic by these guidelines There is no variant in the same codon classified as Pathogenic by these guidelines.
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-04-28
Published on: 2023-05-01
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