Isolated thoracic aortic aneurysm: genes and variants

Genes linked to Isolated thoracic aortic aneurysm

• FBN1: Fibrillin-1

  Its fibrillin-1 microfibrils provide mechanical support to elastic tissues and regulate local availability of growth factors such as TGF-beta. Pathogenic variants cause Marfan syndrome and related fibrillinopathies affecting the aorta, skeleton, eyes, skin, and lungs.

  12 disease-causing and 8 uncertain variants in FBN1 are linked to Isolated thoracic aortic aneurysm.

• ACTA2: Actin, aortic smooth muscle

  Its smooth-muscle actin filaments generate contractile force in arteries and visceral organs and help maintain vascular-wall structure. Pathogenic variants are an important cause of familial thoracic aortic aneurysm and dissection and can also produce occlusive vascular disease.

  1 disease-causing and 2 uncertain variants in ACTA2 are linked to Isolated thoracic aortic aneurysm.

• MYH11: Myosin-11

  Its smooth-muscle myosin motor generates contractile force in arteries and visceral organs. Pathogenic variants can impair aortic smooth-muscle mechanics and cause familial thoracic aortic aneurysm and dissection, sometimes with patent ductus arteriosus.

  0 disease-causing and 7 uncertain variants in MYH11 are linked to Isolated thoracic aortic aneurysm.

Weakly linked (only a few uncertain records): COL3A1, TGFBR2, SMAD3, TGFBR1 and TGFB2.

Known disease-causing variants in Isolated thoracic aortic aneurysm

Which prediction tools work for Isolated thoracic aortic aneurysm

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• AlphaMissense: 100 out of 100
• MetaLR: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100
• MutPred2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Marfan syndrome is also caused by FBN1 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (434 disease-causing).
• Familial thoracic aortic aneurysm and aortic dissection is also caused by FBN1 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (406 disease-causing).
• Marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections is also caused by FBN1 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (10 disease-causing).
• Acromicric dysplasia is also caused by FBN1 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (6 disease-causing).
• Ectopia lentis 1, isolated, autosomal dominant is also caused by FBN1 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (6 disease-causing).
• Aortic aneurysm, familial thoracic 7 is also caused by ACTA2 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (20 disease-causing).
• Familial thoracic aortic aneurysm and aortic dissection is also caused by ACTA2 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (8 disease-causing).
• Multisystemic smooth muscle dysfunction syndrome is also caused by ACTA2 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (6 disease-causing).
• Familial aortopathy is also caused by ACTA2 variants; they fall mostly in different places as the Isolated thoracic aortic aneurysm variants (5 disease-causing).

Diseases related to Isolated thoracic aortic aneurysm

• Familial thoracic aortic aneurysm and aortic dissection, also linked to ACTA2, FBN1 and MYH11
• Aortic aneurysm, familial thoracic 7, also linked to ACTA2 and MYH11
• Connective tissue disorder, also linked to FBN1 and MYH11
• Familial aortopathy, also linked to ACTA2 and FBN1
• Marfan syndrome, also linked to FBN1
• Perrault syndrome, also linked to FBN1
• Marfan syndrome/loeys-dietz syndrome/familial thoracic aortic aneurysms and dissections, also linked to FBN1
• Ectopia lentis 1, isolated, autosomal dominant, also linked to FBN1
• Acromicric dysplasia, also linked to FBN1
• Geleophysic dysplasia, also linked to FBN1
• Multisystemic smooth muscle dysfunction syndrome, also linked to ACTA2
• Thoracic aortic aneurysm or dissection, also linked to ACTA2

Frequently asked questions

Which genes are linked to Isolated thoracic aortic aneurysm?

In CATVariant, Isolated thoracic aortic aneurysm is linked to 3 analyzed proteins: FBN1 (Fibrillin-1), ACTA2 (Actin, aortic smooth muscle) and MYH11 (Myosin-11).

How many genetic variants are linked to Isolated thoracic aortic aneurysm?

43 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 30 are of uncertain significance or have conflicting reports.

Which uncertain variants in Isolated thoracic aortic aneurysm look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Isolated thoracic aortic aneurysm?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 13 disease-causing and 17 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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