Myofibromatosis, infantile, 2: genes and variants

Genes linked to Myofibromatosis, infantile, 2

• NOTCH3: Neurogenic locus notch homolog protein 3

  Its signaling helps maintain vascular smooth-muscle and mural-cell identity in small arteries. Pathogenic cysteine-altering variants cause CADASIL, with migraine, recurrent ischemic strokes, white-matter disease, and progressive cognitive impairment.

  12 disease-causing and 27 uncertain variants in NOTCH3 are linked to Myofibromatosis, infantile, 2.

• PDGFRB: Platelet-derived growth factor receptor beta

  Its signaling supports pericytes, vascular smooth-muscle cells, and other mesenchymal lineages during growth and tissue repair. Oncogenic fusions drive myeloid neoplasms, while germline activating or loss-of-function variants can cause developmental and vascular disorders.

  4 disease-causing and 4 uncertain variants in PDGFRB are linked to Myofibromatosis, infantile, 2.

Where Myofibromatosis, infantile, 2 variants cluster

• NOTCH3 EGF-like 3 (positions 119–156): 3 of 12 disease-causing changes, 15.3× more than its size predicts.

Known disease-causing variants in Myofibromatosis, infantile, 2

Which prediction tools work for Myofibromatosis, infantile, 2

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

• REVEL: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 85 out of 100
• PolyPhen-2: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 75 out of 100
• phyloP: 65 out of 100

Same protein, different disease

• Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 is also caused by NOTCH3 variants; they fall mostly in different places as the Myofibromatosis, infantile, 2 variants (89 disease-causing).
• Infantile myofibromatosis is also caused by PDGFRB variants; they fall partly in the same places as the Myofibromatosis, infantile, 2 variants (8 disease-causing).
• Acroosteolysis-keloid-like lesions-premature aging syndrome is also caused by PDGFRB variants; they fall in the same places as the Myofibromatosis, infantile, 2 variants (6 disease-causing).
• Skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome is also caused by PDGFRB variants; they fall mostly in different places as the Myofibromatosis, infantile, 2 variants (4 disease-causing).

Diseases related to Myofibromatosis, infantile, 2

• Gastrointestinal stromal tumor, also linked to PDGFRB
• Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, also linked to NOTCH3
• Acute myeloid leukemia, also linked to PDGFRB
• Colorectal cancer, also linked to PDGFRB
• Non-small cell lung carcinoma, also linked to PDGFRB
• Auditory neuropathy, also linked to NOTCH3
• Idiopathic pulmonary fibrosis, also linked to PDGFRB
• Lateral meningocele syndrome, also linked to NOTCH3
• Adams-Oliver syndrome, also linked to NOTCH3
• Infantile myofibromatosis, also linked to PDGFRB
• Hepatocellular carcinoma, also linked to PDGFRB
• Acroosteolysis-keloid-like lesions-premature aging syndrome, also linked to PDGFRB

Frequently asked questions

Which genes are linked to Myofibromatosis, infantile, 2?

In CATVariant, Myofibromatosis, infantile, 2 is linked to 2 analyzed proteins: NOTCH3 (Neurogenic locus notch homolog protein 3) and PDGFRB (Platelet-derived growth factor receptor beta).

How many genetic variants are linked to Myofibromatosis, infantile, 2?

64 variants: 16 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 31 are of uncertain significance or have conflicting reports.

Which uncertain variants in Myofibromatosis, infantile, 2 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 Myofibromatosis, infantile, 2?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.85, based on 11 disease-causing and 168 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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