TABLE I.
Summary of Variants Ranked by pVAAST/Phevor Showing Pathogenicity Predictions of Four In Silico Algorithms
| Gene | Phevor rank |
pVAAST rank |
Variant (transcript level) |
Variant (protein level) |
AlignGVD score |
SIFT score | Polyphen2 score |
MutationTaster score |
|---|---|---|---|---|---|---|---|---|
| MYH6 | 1 | 2 |
NM_002471.3: c.5653G>A |
p. Glu1885Lys |
C55 | Deleterious (0.00) |
Possibly damaging (0.716) |
Disease causing (1.0) |
| LAMB2 | 2 | 17 |
NM_002292.3: c.1750C>T |
p. Arg584Cys |
C65 | Deleterious (0.00) |
Probably damaging (0.997) |
Disease causing (1.0) |
| CCDC154 | 3 | 8 |
NM_001143980.1: c.959T>A |
p. Leu320Gln |
C65 | Deleterious (0.00) |
Probably damaging (0.999) |
Polymorphism (0.940) |
| IFRD2 | 5 | 3 |
NM_006764.4: c.1175G>A |
p. Arg392His |
C0 | Tolerated (0.10) |
Probably damaging (0.945) |
Disease causing (0.983) |
| DIP2A | 8 | 1 |
NM_015151.3: c.3319C>T |
p. Arg1107Trp |
C0 | Deleterious (0.01) |
Probably damaging (0.948) |
Disease causing (0.995) |
| SIGLEC11 | 9 | 18 |
NM_052884.2: c.342C>G |
p. Cys114Trp |
C15 | Deleterious (0.00) |
Probably damaging (1.000) |
Disease causing (1.0) |
| LTF | 22 | 16 |
NM_002343.3: c.293C>T |
p.Ala98Val | C0 | Tolerated (0.07) |
Possibly damaging (0.689) |
Polymorphism (0.554) |
| FUZ | 32 | 6 |
NM_025129.4: c.272C>T |
p.Ser91Phe | C0 | Deleterious (0.02) |
Probably damaging (0.946) |
Disease causing (0.998) |
| INTU | 33 | 23 |
NM_015693.3: c.2512T>C: rs144025772 |
p. Cys838Arg |
C0 | Deleterious (0.01) |
Probably damaging (0.974) |
Disease causing (1.000) |
| MYH14 | 42 | 15 |
NM_001145809.1: c.1919G>A: rs199696801 |
p. Arg640Gln |
C0 | Deleterious (0.04) |
Benign (0.055) |
Polymorphism (0.934) |
| KCNE2 | - | - |
NM_172201.1: c.170T>C: rs74315448 |
p.lle57Thr | C65 | Deleterious (0.00) |
Probably damaging (0.918) |
Disease causing (0.999) |
Note: AlignGVD scores variants on a scale C0, C15, C25, C35, C45, C55, C65, with CG5 representing the highest risk allele. The KCNE2 variant was not ranked by Phevor but was considered a candidate variant because of its association with Long OT syndrome [Abbott et al., 1999] and is present in ClinVar as a disease-causing variant (http://www.ncbi.nlm.nih.gov/clinvar/RCV000006426/).