Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24864 | 74815;74816;74817 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| N2AB | 23223 | 69892;69893;69894 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| N2A | 22296 | 67111;67112;67113 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| N2B | 15799 | 47620;47621;47622 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| Novex-1 | 15924 | 47995;47996;47997 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| Novex-2 | 15991 | 48196;48197;48198 | chr2:178571542;178571541;178571540 | chr2:179436269;179436268;179436267 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.979 | N | 0.534 | 0.286 | 0.32980341726 | gnomAD-4.0.0 | 1.5924E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-05 |
| A/T | rs1216441388  |
-0.421 | 0.958 | N | 0.586 | 0.21 | 0.292787519742 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.97E-06 | 0 |
| A/T | rs1216441388 |
-0.421 | 0.958 | N | 0.586 | 0.21 | 0.292787519742 | gnomAD-4.0.0 | 1.59248E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85958E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.8263 | likely_pathogenic | 0.8356 | pathogenic | -0.806 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | N |
| A/D | 0.9881 | likely_pathogenic | 0.9887 | pathogenic | -0.384 | Destabilizing | 0.998 | D | 0.617 | neutral | None | None | None | None | N |
| A/E | 0.9704 | likely_pathogenic | 0.9708 | pathogenic | -0.477 | Destabilizing | 0.994 | D | 0.675 | prob.neutral | N | 0.467063144 | None | None | N |
| A/F | 0.894 | likely_pathogenic | 0.8762 | pathogenic | -0.804 | Destabilizing | 0.991 | D | 0.643 | neutral | None | None | None | None | N |
| A/G | 0.6494 | likely_pathogenic | 0.665 | pathogenic | -0.653 | Destabilizing | 0.979 | D | 0.534 | neutral | N | 0.489870835 | None | None | N |
| A/H | 0.9708 | likely_pathogenic | 0.9697 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.605 | neutral | None | None | None | None | N |
| A/I | 0.7598 | likely_pathogenic | 0.7298 | pathogenic | -0.269 | Destabilizing | 0.938 | D | 0.639 | neutral | None | None | None | None | N |
| A/K | 0.9808 | likely_pathogenic | 0.9799 | pathogenic | -0.838 | Destabilizing | 0.995 | D | 0.679 | prob.neutral | None | None | None | None | N |
| A/L | 0.5604 | ambiguous | 0.5353 | ambiguous | -0.269 | Destabilizing | 0.938 | D | 0.551 | neutral | None | None | None | None | N |
| A/M | 0.722 | likely_pathogenic | 0.6996 | pathogenic | -0.401 | Destabilizing | 0.999 | D | 0.658 | neutral | None | None | None | None | N |
| A/N | 0.9225 | likely_pathogenic | 0.9223 | pathogenic | -0.547 | Destabilizing | 0.998 | D | 0.646 | neutral | None | None | None | None | N |
| A/P | 0.7957 | likely_pathogenic | 0.8044 | pathogenic | -0.307 | Destabilizing | 0.998 | D | 0.669 | neutral | N | 0.489908121 | None | None | N |
| A/Q | 0.9064 | likely_pathogenic | 0.9021 | pathogenic | -0.731 | Destabilizing | 0.998 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/R | 0.9519 | likely_pathogenic | 0.9504 | pathogenic | -0.45 | Destabilizing | 0.995 | D | 0.671 | neutral | None | None | None | None | N |
| A/S | 0.3189 | likely_benign | 0.3236 | benign | -0.853 | Destabilizing | 0.979 | D | 0.504 | neutral | N | 0.471725005 | None | None | N |
| A/T | 0.5647 | likely_pathogenic | 0.5623 | ambiguous | -0.846 | Destabilizing | 0.958 | D | 0.586 | neutral | N | 0.476437391 | None | None | N |
| A/V | 0.6062 | likely_pathogenic | 0.5689 | pathogenic | -0.307 | Destabilizing | 0.142 | N | 0.3 | neutral | N | 0.495372656 | None | None | N |
| A/W | 0.9822 | likely_pathogenic | 0.9812 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| A/Y | 0.9504 | likely_pathogenic | 0.9471 | pathogenic | -0.647 | Destabilizing | 0.995 | D | 0.643 | neutral | None | None | None | None | N |
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.