Table 3:
Topics with high total scores (11-12) on the ClinGen AWG semi-quantitative metric
| Disorder | Disorder OMIM(s) | On ACMG SF v2.0 List | Gene(s) | Outcome | Intervention | Severity | Likelihood | Effectiveness | Nature of the Intervention | Total | Likelihood Evidence Level | Effectiveness Evidence Level |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Loeys-Dietz Syndrome | 609192 610168 613795 614816 615582 |
Yes |
TGFBR1 TGFBR2 SMAD3 TGFB2† TGFB3† |
Clinically Significant Aortic Aneurysm | Surveillance | 3 | 3 | 3 | 3 | 12 | C | B |
| Marfan Syndrome | 154700 | Yes | FBN1 | Clinically Significant Aortic Aneurysms | Surveillance | 3 | 3 | 3 | 3 | 12 | C | B |
| Aortic Dilation Progression | Beta-blockers | 3 | 3 | 3 | 3 | 12 | C | A | ||||
| Adrenoleukodystrophy | 300100 | No | ABCD1 | Neurological/Cognitive decline | Neurological surveillance to plan initiation of hematopoietic cell transplantation | 2 | 3 | 3 | 3 | 11 | C | C |
| Biotinidase Deficiency | 253260 | No | BTD | Neurological complications | Biotin therapy | 2 | 3 | 3 | 3 | 11 | C | C |
| Dopa-responsive dystonia (autosomal dominant) | 128230 | No | GCH1 | Neuromuscular dysfunction | Levodopa therapy | 2 | 3 | 3 | 3 | 11 | C | C |
| Familial Hypercholesterolemia (Heterozygous) | 143890 144010 603776 |
Yes |
LDLR APOB PCSK9 |
High cholesterol | Statins | 2 | 3 | 3 | 3 | 11 | C | A |
| Familial Hypercholesterolemia (Homozygous) | 143890 144010 603776 |
Yes |
LDLR APOB PCSK9 |
High cholesterol | Statins | 2 | 3 | 3 | 3 | 11 | C | A |
| Familial Hyperparathyroidism and Parathyroid Carcinoma | 145000 145001 608266 |
No | CDC73 | Morbidity from primary hyperparathyroidism | Surveillance of parathyroid hormone and calcium | 2 | 3 | 3 | 3 | 11 | C | C |
| Familial Thoracic Aortic Aneurysms and Dissections | 132900 611788 154700 609192 610168 613795 613780 |
Yes |
MYH11 ACTA2 FBN1 TGFBR1 TGFBR2 SMAD3 MYLK† |
Clinically significant aortic aneurysm | Aortic surveillance | 3 | 2 | 3 | 3 | 11 | D | C |
| Aortic dilation progression | Beta blockers | 3 | 2 | 3 | 3 | 11 | D | C | ||||
| Hereditary Hemorrhagic Telangiectasia | 600376 187300 615506 175050 |
No | ENG | Anticipatory treatment to avoid pulmonary arteriovenous malformation-related morbidity | Transthoracic contrast echocardiography | 2 | 3 | 3 | 3 | 11 | E | B |
| SMAD4 | Anticipatory treatment to avoid pulmonary arteriovenous malformation-related morbidity | Transthoracic contrast echocardiography | 2 | 3 | 3 | 3 | 11 | E | B | |||
| Maturity Onset Diabetes of the Young, Type 3 (MODY3) | 600496 | No | HNF1A | Suboptimal glycemic control | Sulfonylureas/ optimal diabetic control | 2 | 3 | 3 | 3 | 11 | C | C |
| Multiple endocrine neoplasia type IIA, Familial medullary thyroid cancer | 171400 155240 |
Yes | RET | Pheochromocytoma | Biochemical screening | 2 | 3 | 3 | 3 | 11 | C | B |
| Multiple Endocrine Neoplasia Type IIB | 162300 | Yes | RET | Pheochromocytoma | Biochemical screening | 2 | 3 | 3 | 3 | 11 | C | B |
| Peutz-Jeghers syndrome | 175200 | Yes | STK11 | Colorectal Cancer | Cancer-Specific Surveillance | 2 | 3 | 3 | 3 | 11 | A | B |
| Von Hippel-Lindau Syndrome | 193300 | Yes | VHL | Renal cell carcinoma | Surveillance | 2 | 3 | 3 | 3 | 11 | C | C |
† Gene not included on the ACMG SF v2.0 list for this disorder.