Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1089 | 3490;3491;3492 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| N2AB | 1089 | 3490;3491;3492 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| N2A | 1089 | 3490;3491;3492 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| N2B | 1043 | 3352;3353;3354 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| Novex-1 | 1043 | 3352;3353;3354 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| Novex-2 | 1043 | 3352;3353;3354 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
| Novex-3 | 1089 | 3490;3491;3492 | chr2:178782327;178782326;178782325 | chr2:179647054;179647053;179647052 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs1222071933  |
-0.326 | 0.017 | N | 0.155 | 0.071 | 0.242825505644 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.41026E-04 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs1222071933 |
-0.326 | 0.017 | N | 0.155 | 0.071 | 0.242825505644 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1222071933 |
-0.326 | 0.017 | N | 0.155 | 0.071 | 0.242825505644 | gnomAD-4.0.0 | 1.31439E-05 | None | None | None | None | I | None | 2.41324E-05 | 0 | None | 0 | 1.92604E-04 | None | 0 | 0 | 0 | 0 | 0 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0947 | likely_benign | 0.0937 | benign | -0.657 | Destabilizing | 0.003 | N | 0.077 | neutral | N | 0.474424377 | None | None | I |
| V/C | 0.7483 | likely_pathogenic | 0.7425 | pathogenic | -0.679 | Destabilizing | 0.94 | D | 0.308 | neutral | None | None | None | None | I |
| V/D | 0.2118 | likely_benign | 0.2095 | benign | -0.31 | Destabilizing | 0.418 | N | 0.38 | neutral | None | None | None | None | I |
| V/E | 0.1452 | likely_benign | 0.1456 | benign | -0.381 | Destabilizing | 0.213 | N | 0.337 | neutral | N | 0.447469764 | None | None | I |
| V/F | 0.1445 | likely_benign | 0.1417 | benign | -0.639 | Destabilizing | 0.716 | D | 0.367 | neutral | None | None | None | None | I |
| V/G | 0.1539 | likely_benign | 0.1507 | benign | -0.845 | Destabilizing | 0.002 | N | 0.204 | neutral | N | 0.493028644 | None | None | I |
| V/H | 0.4309 | ambiguous | 0.4269 | ambiguous | -0.338 | Destabilizing | 0.836 | D | 0.301 | neutral | None | None | None | None | I |
| V/I | 0.0788 | likely_benign | 0.0801 | benign | -0.29 | Destabilizing | 0.002 | N | 0.137 | neutral | None | None | None | None | I |
| V/K | 0.2004 | likely_benign | 0.1937 | benign | -0.594 | Destabilizing | 0.264 | N | 0.362 | neutral | None | None | None | None | I |
| V/L | 0.1294 | likely_benign | 0.1246 | benign | -0.29 | Destabilizing | 0.017 | N | 0.163 | neutral | N | 0.486070261 | None | None | I |
| V/M | 0.0888 | likely_benign | 0.0868 | benign | -0.436 | Destabilizing | 0.017 | N | 0.155 | neutral | N | 0.499653206 | None | None | I |
| V/N | 0.1685 | likely_benign | 0.1663 | benign | -0.389 | Destabilizing | 0.418 | N | 0.401 | neutral | None | None | None | None | I |
| V/P | 0.5323 | ambiguous | 0.4655 | ambiguous | -0.377 | Destabilizing | 0.593 | D | 0.386 | neutral | None | None | None | None | I |
| V/Q | 0.1893 | likely_benign | 0.1841 | benign | -0.576 | Destabilizing | 0.061 | N | 0.208 | neutral | None | None | None | None | I |
| V/R | 0.1872 | likely_benign | 0.1805 | benign | -0.109 | Destabilizing | 0.418 | N | 0.403 | neutral | None | None | None | None | I |
| V/S | 0.1144 | likely_benign | 0.1137 | benign | -0.793 | Destabilizing | 0.027 | N | 0.195 | neutral | None | None | None | None | I |
| V/T | 0.1041 | likely_benign | 0.103 | benign | -0.758 | Destabilizing | 0.004 | N | 0.084 | neutral | None | None | None | None | I |
| V/W | 0.7561 | likely_pathogenic | 0.7445 | pathogenic | -0.75 | Destabilizing | 0.983 | D | 0.299 | neutral | None | None | None | None | I |
| V/Y | 0.4909 | ambiguous | 0.4858 | ambiguous | -0.453 | Destabilizing | 0.836 | D | 0.333 | 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.