ELN
Chr 7ADelastin
Also known as: ADCL1, SVAS, WBS, WS
Elastin is a major structural protein that provides elasticity to tissues including blood vessels, skin, lungs, and ligaments, and plays a critical role in late arterial morphogenesis by stabilizing arterial structure and regulating vascular smooth muscle organization. Mutations cause autosomal dominant supravalvular aortic stenosis and cutis laxa, affecting cardiovascular and connective tissue systems. This gene is not highly constrained against loss-of-function variants.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 21 | 1 | 9 | 0 | 31 |
Likely Pathogenic | 20 | 0 | 0 | 0 | 20 |
VUS | 7 | 125 | 30 | 4 | 166 |
Likely Benign | 1 | 7 | 74 | 67 | 149 |
Benign | 0 | 0 | 4 | 1 | 5 |
Conflicting | — | 4 | |||
| Total | 49 | 133 | 117 | 72 | 375 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ELN · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
ACTIVE NOT RECRUITINGAsciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase
RECRUITINGRevumenib in Combination With 7+3 + Midostaurin in AML
RECRUITINGSafety and Efficacy of GYA01 (CART84) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Acute Lymphoblastic T Leukemia Patients (T-ALL).
RECRUITINGOral-ATO for TP53-mutated Myeloid Malignancies
RECRUITINGOBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
RECRUITINGTalazoparib for Cohesin-Mutated AML and MDS With Excess Blasts
ACTIVE NOT RECRUITINGToxicity Genetic Determinants and Response to Azacitidine and Venetoclax in AML
RECRUITINGA Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)
ACTIVE NOT RECRUITINGCardiovascular Structure and Function in the Mucopolysaccharidoses
ACTIVE NOT RECRUITINGCharacterization of the Natural History of Microduplication Syndrome 7q11.23
NOT YET RECRUITINGChimeric Antigen Receptor T Cell Redirected to Target CD4 Positive Relapsed Refractory Acute Myeloid Leukemia (AML ) as a Bridge to Allogeneic Stem Cell Transplant
RECRUITINGExternal Resources
Links to major genomics databases and tools