Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15233 | 45922;45923;45924 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| N2AB | 13592 | 40999;41000;41001 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| N2A | 12665 | 38218;38219;38220 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| N2B | 6168 | 18727;18728;18729 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| Novex-1 | 6293 | 19102;19103;19104 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| Novex-2 | 6360 | 19303;19304;19305 | chr2:178620913;178620912;178620911 | chr2:179485640;179485639;179485638 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1267073931  |
0.038 | 0.876 | N | 0.553 | 0.196 | 0.380223377699 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14863E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1267073931 |
0.038 | 0.876 | N | 0.553 | 0.196 | 0.380223377699 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 7.25E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1267073931 |
0.038 | 0.876 | N | 0.553 | 0.196 | 0.380223377699 | gnomAD-4.0.0 | 2.48085E-06 | None | None | None | None | N | None | 4.01091E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48073E-07 | 0 | 0 |
| T/N | None | None | 0.111 | N | 0.33 | 0.121 | 0.283761946502 | gnomAD-4.0.0 | 3.42352E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49942E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.122 | likely_benign | 0.1051 | benign | -0.427 | Destabilizing | 0.454 | N | 0.445 | neutral | N | 0.430315752 | None | None | N |
| T/C | 0.607 | likely_pathogenic | 0.5417 | ambiguous | -0.337 | Destabilizing | 0.998 | D | 0.515 | neutral | None | None | None | None | N |
| T/D | 0.7087 | likely_pathogenic | 0.6032 | pathogenic | 0.11 | Stabilizing | 0.728 | D | 0.529 | neutral | None | None | None | None | N |
| T/E | 0.5152 | ambiguous | 0.4096 | ambiguous | 0.067 | Stabilizing | 0.728 | D | 0.495 | neutral | None | None | None | None | N |
| T/F | 0.516 | ambiguous | 0.4095 | ambiguous | -0.69 | Destabilizing | 0.949 | D | 0.544 | neutral | None | None | None | None | N |
| T/G | 0.4168 | ambiguous | 0.3518 | ambiguous | -0.619 | Destabilizing | 0.842 | D | 0.488 | neutral | None | None | None | None | N |
| T/H | 0.4388 | ambiguous | 0.359 | ambiguous | -0.834 | Destabilizing | 0.993 | D | 0.523 | neutral | None | None | None | None | N |
| T/I | 0.332 | likely_benign | 0.2547 | benign | -0.031 | Destabilizing | 0.876 | D | 0.553 | neutral | N | 0.497472054 | None | None | N |
| T/K | 0.3161 | likely_benign | 0.238 | benign | -0.531 | Destabilizing | 0.016 | N | 0.312 | neutral | None | None | None | None | N |
| T/L | 0.2003 | likely_benign | 0.1595 | benign | -0.031 | Destabilizing | 0.016 | N | 0.307 | neutral | None | None | None | None | N |
| T/M | 0.143 | likely_benign | 0.1161 | benign | 0.031 | Stabilizing | 0.949 | D | 0.54 | neutral | None | None | None | None | N |
| T/N | 0.2745 | likely_benign | 0.2167 | benign | -0.358 | Destabilizing | 0.111 | N | 0.33 | neutral | N | 0.496373883 | None | None | N |
| T/P | 0.5633 | ambiguous | 0.5776 | pathogenic | -0.131 | Destabilizing | 0.966 | D | 0.56 | neutral | N | 0.485490454 | None | None | N |
| T/Q | 0.3463 | ambiguous | 0.2731 | benign | -0.53 | Destabilizing | 0.949 | D | 0.559 | neutral | None | None | None | None | N |
| T/R | 0.2557 | likely_benign | 0.1823 | benign | -0.249 | Destabilizing | 0.904 | D | 0.553 | neutral | None | None | None | None | N |
| T/S | 0.1788 | likely_benign | 0.1475 | benign | -0.587 | Destabilizing | 0.136 | N | 0.317 | neutral | N | 0.44592836 | None | None | N |
| T/V | 0.2367 | likely_benign | 0.192 | benign | -0.131 | Destabilizing | 0.728 | D | 0.481 | neutral | None | None | None | None | N |
| T/W | 0.8029 | likely_pathogenic | 0.737 | pathogenic | -0.69 | Destabilizing | 0.998 | D | 0.55 | neutral | None | None | None | None | N |
| T/Y | 0.5479 | ambiguous | 0.4671 | ambiguous | -0.429 | Destabilizing | 0.991 | D | 0.541 | 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.