Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5421 | 16486;16487;16488 | chr2:178732915;178732914;178732913 | chr2:179597642;179597641;179597640 |
| N2AB | 5104 | 15535;15536;15537 | chr2:178732915;178732914;178732913 | chr2:179597642;179597641;179597640 |
| N2A | 4177 | 12754;12755;12756 | chr2:178732915;178732914;178732913 | chr2:179597642;179597641;179597640 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/T | rs1304285904  |
0.722 | None | N | 0.141 | 0.224 | 0.459729313489 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| M/T | rs1304285904 |
0.722 | None | N | 0.141 | 0.224 | 0.459729313489 | gnomAD-4.0.0 | 2.05305E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69859E-06 | 0 | 0 |
| M/V | rs1353177231 |
0.27 | None | N | 0.125 | 0.148 | 0.163833314356 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1354 | likely_benign | 0.1628 | benign | -0.824 | Destabilizing | None | N | 0.145 | neutral | None | None | None | None | I |
| M/C | 0.5307 | ambiguous | 0.5827 | pathogenic | -0.493 | Destabilizing | 0.316 | N | 0.254 | neutral | None | None | None | None | I |
| M/D | 0.4434 | ambiguous | 0.5256 | ambiguous | 0.077 | Stabilizing | 0.009 | N | 0.343 | neutral | None | None | None | None | I |
| M/E | 0.1885 | likely_benign | 0.2346 | benign | 0.026 | Stabilizing | 0.004 | N | 0.298 | neutral | None | None | None | None | I |
| M/F | 0.2352 | likely_benign | 0.2856 | benign | -0.422 | Destabilizing | 0.004 | N | 0.209 | neutral | None | None | None | None | I |
| M/G | 0.2112 | likely_benign | 0.2475 | benign | -1.02 | Destabilizing | 0.002 | N | 0.335 | neutral | None | None | None | None | I |
| M/H | 0.2662 | likely_benign | 0.306 | benign | -0.191 | Destabilizing | 0.132 | N | 0.34 | neutral | None | None | None | None | I |
| M/I | 0.151 | likely_benign | 0.188 | benign | -0.388 | Destabilizing | None | N | 0.171 | neutral | N | 0.409203961 | None | None | I |
| M/K | 0.0689 | likely_benign | 0.0758 | benign | 0.196 | Stabilizing | None | N | 0.145 | neutral | N | 0.365951829 | None | None | I |
| M/L | 0.0864 | likely_benign | 0.0942 | benign | -0.388 | Destabilizing | None | N | 0.107 | neutral | N | 0.348480789 | None | None | I |
| M/N | 0.2239 | likely_benign | 0.2751 | benign | 0.404 | Stabilizing | 0.009 | N | 0.307 | neutral | None | None | None | None | I |
| M/P | 0.259 | likely_benign | 0.3109 | benign | -0.505 | Destabilizing | 0.018 | N | 0.305 | neutral | None | None | None | None | I |
| M/Q | 0.1175 | likely_benign | 0.1264 | benign | 0.213 | Stabilizing | 0.009 | N | 0.227 | neutral | None | None | None | None | I |
| M/R | 0.0698 | likely_benign | 0.0775 | benign | 0.724 | Stabilizing | 0.003 | N | 0.268 | neutral | N | 0.326028004 | None | None | I |
| M/S | 0.1587 | likely_benign | 0.1905 | benign | -0.08 | Destabilizing | 0.002 | N | 0.252 | neutral | None | None | None | None | I |
| M/T | 0.0844 | likely_benign | 0.0956 | benign | -0.03 | Destabilizing | None | N | 0.141 | neutral | N | 0.410012037 | None | None | I |
| M/V | 0.0618 | likely_benign | 0.068 | benign | -0.505 | Destabilizing | None | N | 0.125 | neutral | N | 0.398005532 | None | None | I |
| M/W | 0.3995 | ambiguous | 0.4635 | ambiguous | -0.358 | Destabilizing | 0.316 | N | 0.243 | neutral | None | None | None | None | I |
| M/Y | 0.3961 | ambiguous | 0.4686 | ambiguous | -0.252 | Destabilizing | None | N | 0.177 | 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.