Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19266 | 58021;58022;58023 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| N2AB | 17625 | 53098;53099;53100 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| N2A | 16698 | 50317;50318;50319 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| N2B | 10201 | 30826;30827;30828 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| Novex-1 | 10326 | 31201;31202;31203 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| Novex-2 | 10393 | 31402;31403;31404 | chr2:178595558;178595557;178595556 | chr2:179460285;179460284;179460283 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/V | rs372963343  |
-0.275 | 0.002 | N | 0.261 | 0.206 | None | gnomAD-2.1.1 | 4.11E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.26397E-04 | None | 0 | 1.07E-05 | 0 |
| M/V | rs372963343 |
-0.275 | 0.002 | N | 0.261 | 0.206 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07125E-04 | 0 |
| M/V | rs372963343 |
-0.275 | 0.002 | N | 0.261 | 0.206 | None | gnomAD-4.0.0 | 2.03583E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.33111E-04 | 4.32231E-06 | 2.80171E-04 | 1.63999E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4322 | ambiguous | 0.4572 | ambiguous | -1.294 | Destabilizing | 0.031 | N | 0.515 | neutral | None | None | None | None | I |
| M/C | 0.6393 | likely_pathogenic | 0.6401 | pathogenic | -1.091 | Destabilizing | 0.864 | D | 0.593 | neutral | None | None | None | None | I |
| M/D | 0.8878 | likely_pathogenic | 0.9116 | pathogenic | 0.021 | Stabilizing | 0.214 | N | 0.629 | neutral | None | None | None | None | I |
| M/E | 0.5797 | likely_pathogenic | 0.635 | pathogenic | 0.043 | Stabilizing | 0.072 | N | 0.627 | neutral | None | None | None | None | I |
| M/F | 0.3279 | likely_benign | 0.3567 | ambiguous | -0.365 | Destabilizing | 0.072 | N | 0.566 | neutral | None | None | None | None | I |
| M/G | 0.736 | likely_pathogenic | 0.7613 | pathogenic | -1.594 | Destabilizing | 0.072 | N | 0.627 | neutral | None | None | None | None | I |
| M/H | 0.5976 | likely_pathogenic | 0.6314 | pathogenic | -0.555 | Destabilizing | 0.356 | N | 0.627 | neutral | None | None | None | None | I |
| M/I | 0.2311 | likely_benign | 0.2599 | benign | -0.544 | Destabilizing | None | N | 0.212 | neutral | N | 0.383007155 | None | None | I |
| M/K | 0.2229 | likely_benign | 0.2485 | benign | -0.111 | Destabilizing | 0.029 | N | 0.5 | neutral | N | 0.429414235 | None | None | I |
| M/L | 0.1129 | likely_benign | 0.131 | benign | -0.544 | Destabilizing | None | N | 0.193 | neutral | N | 0.408710889 | None | None | I |
| M/N | 0.6034 | likely_pathogenic | 0.6508 | pathogenic | -0.023 | Destabilizing | 0.214 | N | 0.627 | neutral | None | None | None | None | I |
| M/P | 0.5879 | likely_pathogenic | 0.6393 | pathogenic | -0.765 | Destabilizing | 0.628 | D | 0.635 | neutral | None | None | None | None | I |
| M/Q | 0.2992 | likely_benign | 0.3074 | benign | -0.098 | Destabilizing | 0.214 | N | 0.581 | neutral | None | None | None | None | I |
| M/R | 0.2125 | likely_benign | 0.237 | benign | 0.345 | Stabilizing | None | N | 0.381 | neutral | N | 0.424835135 | None | None | I |
| M/S | 0.5353 | ambiguous | 0.5746 | pathogenic | -0.664 | Destabilizing | 0.072 | N | 0.523 | neutral | None | None | None | None | I |
| M/T | 0.2821 | likely_benign | 0.3084 | benign | -0.521 | Destabilizing | 0.055 | N | 0.529 | neutral | N | 0.413175347 | None | None | I |
| M/V | 0.0924 | likely_benign | 0.0974 | benign | -0.765 | Destabilizing | 0.002 | N | 0.261 | neutral | N | 0.366690909 | None | None | I |
| M/W | 0.6498 | likely_pathogenic | 0.6822 | pathogenic | -0.285 | Destabilizing | 0.864 | D | 0.589 | neutral | None | None | None | None | I |
| M/Y | 0.6101 | likely_pathogenic | 0.6468 | pathogenic | -0.261 | Destabilizing | 0.356 | N | 0.617 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.