Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19624 | 59095;59096;59097 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| N2AB | 17983 | 54172;54173;54174 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| N2A | 17056 | 51391;51392;51393 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| N2B | 10559 | 31900;31901;31902 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| Novex-1 | 10684 | 32275;32276;32277 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| Novex-2 | 10751 | 32476;32477;32478 | chr2:178593338;178593337;178593336 | chr2:179458065;179458064;179458063 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/L | None | None | 0.023 | N | 0.399 | 0.154 | 0.344251166708 | gnomAD-4.0.0 | 6.84365E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65689E-05 |
| R/P | None | None | 0.705 | N | 0.423 | 0.273 | 0.358744678677 | gnomAD-4.0.0 | 6.84365E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65689E-05 |
| R/Q | rs1224706842  |
0.035 | 0.566 | N | 0.448 | 0.176 | 0.178374595973 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs1224706842 |
0.035 | 0.566 | N | 0.448 | 0.176 | 0.178374595973 | gnomAD-4.0.0 | 6.15929E-06 | None | None | None | None | I | None | 2.98989E-05 | 2.23754E-05 | None | 0 | 2.52385E-05 | None | 0 | 0 | 3.59847E-06 | 0 | 3.31378E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7077 | likely_pathogenic | 0.7231 | pathogenic | 0.03 | Stabilizing | 0.035 | N | 0.458 | neutral | None | None | None | None | I |
| R/C | 0.4734 | ambiguous | 0.454 | ambiguous | -0.218 | Destabilizing | 0.935 | D | 0.379 | neutral | None | None | None | None | I |
| R/D | 0.8717 | likely_pathogenic | 0.8777 | pathogenic | -0.286 | Destabilizing | 0.38 | N | 0.428 | neutral | None | None | None | None | I |
| R/E | 0.7006 | likely_pathogenic | 0.7003 | pathogenic | -0.249 | Destabilizing | 0.081 | N | 0.451 | neutral | None | None | None | None | I |
| R/F | 0.7153 | likely_pathogenic | 0.7516 | pathogenic | -0.291 | Destabilizing | 0.38 | N | 0.396 | neutral | None | None | None | None | I |
| R/G | 0.6089 | likely_pathogenic | 0.5794 | pathogenic | -0.103 | Destabilizing | 0.251 | N | 0.439 | neutral | N | 0.4956793 | None | None | I |
| R/H | 0.2329 | likely_benign | 0.2248 | benign | -0.581 | Destabilizing | 0.555 | D | 0.429 | neutral | None | None | None | None | I |
| R/I | 0.3779 | ambiguous | 0.4268 | ambiguous | 0.335 | Stabilizing | 0.001 | N | 0.373 | neutral | None | None | None | None | I |
| R/K | 0.2044 | likely_benign | 0.1838 | benign | -0.147 | Destabilizing | 0.001 | N | 0.268 | neutral | None | None | None | None | I |
| R/L | 0.4463 | ambiguous | 0.466 | ambiguous | 0.335 | Stabilizing | 0.023 | N | 0.399 | neutral | N | 0.44733078 | None | None | I |
| R/M | 0.497 | ambiguous | 0.4999 | ambiguous | -0.07 | Destabilizing | 0.016 | N | 0.401 | neutral | None | None | None | None | I |
| R/N | 0.7558 | likely_pathogenic | 0.7793 | pathogenic | -0.031 | Destabilizing | 0.38 | N | 0.429 | neutral | None | None | None | None | I |
| R/P | 0.8947 | likely_pathogenic | 0.8894 | pathogenic | 0.251 | Stabilizing | 0.705 | D | 0.423 | neutral | N | 0.474736146 | None | None | I |
| R/Q | 0.2431 | likely_benign | 0.2359 | benign | -0.08 | Destabilizing | 0.566 | D | 0.448 | neutral | N | 0.515766571 | None | None | I |
| R/S | 0.7844 | likely_pathogenic | 0.8087 | pathogenic | -0.217 | Destabilizing | 0.081 | N | 0.485 | neutral | None | None | None | None | I |
| R/T | 0.54 | ambiguous | 0.5495 | ambiguous | -0.079 | Destabilizing | 0.149 | N | 0.484 | neutral | None | None | None | None | I |
| R/V | 0.5216 | ambiguous | 0.5714 | pathogenic | 0.251 | Stabilizing | 0.029 | N | 0.421 | neutral | None | None | None | None | I |
| R/W | 0.3487 | ambiguous | 0.3234 | benign | -0.473 | Destabilizing | 0.935 | D | 0.433 | neutral | None | None | None | None | I |
| R/Y | 0.5378 | ambiguous | 0.5506 | ambiguous | -0.07 | Destabilizing | 0.555 | D | 0.397 | 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.