Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19467 | 58624;58625;58626 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| N2AB | 17826 | 53701;53702;53703 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| N2A | 16899 | 50920;50921;50922 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| N2B | 10402 | 31429;31430;31431 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| Novex-1 | 10527 | 31804;31805;31806 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| Novex-2 | 10594 | 32005;32006;32007 | chr2:178593994;178593993;178593992 | chr2:179458721;179458720;179458719 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | rs920055688  |
None | 0.984 | N | 0.468 | 0.499 | 0.426084969639 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | I | None | 2.98864E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15953E-05 | 0 |
| S/T | rs920055688 |
None | 0.046 | N | 0.211 | 0.077 | 0.208000267992 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs920055688 |
None | 0.046 | N | 0.211 | 0.077 | 0.208000267992 | gnomAD-4.0.0 | 3.7187E-06 | None | None | None | None | I | None | 1.33486E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23846E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0926 | likely_benign | 0.0985 | benign | -0.388 | Destabilizing | 0.026 | N | 0.231 | neutral | N | 0.50435279 | None | None | I |
| S/C | 0.0939 | likely_benign | 0.1077 | benign | -0.377 | Destabilizing | 0.999 | D | 0.499 | neutral | N | 0.521500127 | None | None | I |
| S/D | 0.497 | ambiguous | 0.5444 | ambiguous | 0.024 | Stabilizing | 0.959 | D | 0.419 | neutral | None | None | None | None | I |
| S/E | 0.4336 | ambiguous | 0.4693 | ambiguous | -0.056 | Destabilizing | 0.919 | D | 0.429 | neutral | None | None | None | None | I |
| S/F | 0.1539 | likely_benign | 0.1635 | benign | -0.861 | Destabilizing | 0.995 | D | 0.614 | neutral | N | 0.503395872 | None | None | I |
| S/G | 0.1377 | likely_benign | 0.1435 | benign | -0.531 | Destabilizing | 0.851 | D | 0.426 | neutral | None | None | None | None | I |
| S/H | 0.2986 | likely_benign | 0.3302 | benign | -1.043 | Destabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | I |
| S/I | 0.1347 | likely_benign | 0.1494 | benign | -0.14 | Destabilizing | 0.976 | D | 0.596 | neutral | None | None | None | None | I |
| S/K | 0.5245 | ambiguous | 0.575 | pathogenic | -0.638 | Destabilizing | 0.919 | D | 0.429 | neutral | None | None | None | None | I |
| S/L | 0.0937 | likely_benign | 0.1012 | benign | -0.14 | Destabilizing | 0.919 | D | 0.581 | neutral | None | None | None | None | I |
| S/M | 0.1646 | likely_benign | 0.1792 | benign | 0.04 | Stabilizing | 0.999 | D | 0.476 | neutral | None | None | None | None | I |
| S/N | 0.158 | likely_benign | 0.1804 | benign | -0.377 | Destabilizing | 0.959 | D | 0.466 | neutral | None | None | None | None | I |
| S/P | 0.7207 | likely_pathogenic | 0.7496 | pathogenic | -0.192 | Destabilizing | 0.984 | D | 0.468 | neutral | N | 0.509890332 | None | None | I |
| S/Q | 0.3756 | ambiguous | 0.4106 | ambiguous | -0.61 | Destabilizing | 0.988 | D | 0.391 | neutral | None | None | None | None | I |
| S/R | 0.4611 | ambiguous | 0.499 | ambiguous | -0.428 | Destabilizing | 0.988 | D | 0.472 | neutral | None | None | None | None | I |
| S/T | 0.0783 | likely_benign | 0.0851 | benign | -0.455 | Destabilizing | 0.046 | N | 0.211 | neutral | N | 0.481091928 | None | None | I |
| S/V | 0.1461 | likely_benign | 0.1622 | benign | -0.192 | Destabilizing | 0.851 | D | 0.607 | neutral | None | None | None | None | I |
| S/W | 0.301 | likely_benign | 0.3088 | benign | -0.865 | Destabilizing | 0.999 | D | 0.684 | prob.neutral | None | None | None | None | I |
| S/Y | 0.1584 | likely_benign | 0.167 | benign | -0.6 | Destabilizing | 0.995 | D | 0.613 | neutral | N | 0.503142383 | 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.