Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19930 | 60013;60014;60015 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| N2AB | 18289 | 55090;55091;55092 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| N2A | 17362 | 52309;52310;52311 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| N2B | 10865 | 32818;32819;32820 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| Novex-1 | 10990 | 33193;33194;33195 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| Novex-2 | 11057 | 33394;33395;33396 | chr2:178592116;178592115;178592114 | chr2:179456843;179456842;179456841 |
| 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/A | rs200290906  |
None | 0.76 | N | 0.396 | 0.096 | 0.19670166235 | gnomAD-4.0.0 | 6.84524E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99656E-07 | 0 | 0 |
| T/I | rs748016514 |
0.006 | 0.991 | N | 0.701 | 0.351 | 0.368743488249 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| T/I | rs748016514 |
0.006 | 0.991 | N | 0.701 | 0.351 | 0.368743488249 | gnomAD-4.0.0 | 4.10724E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.95814E-05 | 0 |
| T/P | rs200290906 |
-0.181 | 0.991 | N | 0.698 | 0.246 | 0.307648195649 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| T/P | rs200290906 |
-0.181 | 0.991 | N | 0.698 | 0.246 | 0.307648195649 | gnomAD-4.0.0 | 6.84524E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99656E-07 | 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 | 0.0679 | likely_benign | 0.0667 | benign | -0.479 | Destabilizing | 0.76 | D | 0.396 | neutral | N | 0.430630531 | None | None | N |
| T/C | 0.3884 | ambiguous | 0.3619 | ambiguous | -0.179 | Destabilizing | 0.999 | D | 0.66 | neutral | None | None | None | None | N |
| T/D | 0.5074 | ambiguous | 0.4793 | ambiguous | -0.034 | Destabilizing | 0.986 | D | 0.657 | neutral | None | None | None | None | N |
| T/E | 0.4742 | ambiguous | 0.4706 | ambiguous | -0.125 | Destabilizing | 0.986 | D | 0.655 | neutral | None | None | None | None | N |
| T/F | 0.2549 | likely_benign | 0.238 | benign | -1.085 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/G | 0.1883 | likely_benign | 0.1741 | benign | -0.578 | Destabilizing | 0.91 | D | 0.549 | neutral | None | None | None | None | N |
| T/H | 0.3216 | likely_benign | 0.2996 | benign | -0.992 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | N |
| T/I | 0.2076 | likely_benign | 0.2077 | benign | -0.337 | Destabilizing | 0.991 | D | 0.701 | prob.neutral | N | 0.514171847 | None | None | N |
| T/K | 0.4033 | ambiguous | 0.3944 | ambiguous | -0.311 | Destabilizing | 0.982 | D | 0.66 | neutral | N | 0.454448753 | None | None | N |
| T/L | 0.1273 | likely_benign | 0.1239 | benign | -0.337 | Destabilizing | 0.953 | D | 0.581 | neutral | None | None | None | None | N |
| T/M | 0.1148 | likely_benign | 0.1097 | benign | 0.088 | Stabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| T/N | 0.1277 | likely_benign | 0.1197 | benign | -0.069 | Destabilizing | 0.986 | D | 0.609 | neutral | None | None | None | None | N |
| T/P | 0.1476 | likely_benign | 0.1486 | benign | -0.358 | Destabilizing | 0.991 | D | 0.698 | prob.neutral | N | 0.480477774 | None | None | N |
| T/Q | 0.3068 | likely_benign | 0.3055 | benign | -0.388 | Destabilizing | 0.993 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/R | 0.3604 | ambiguous | 0.3504 | ambiguous | -0.024 | Destabilizing | 0.982 | D | 0.7 | prob.neutral | N | 0.480347275 | None | None | N |
| T/S | 0.0874 | likely_benign | 0.0827 | benign | -0.263 | Destabilizing | 0.17 | N | 0.18 | neutral | N | 0.420469465 | None | None | N |
| T/V | 0.1406 | likely_benign | 0.138 | benign | -0.358 | Destabilizing | 0.953 | D | 0.521 | neutral | None | None | None | None | N |
| T/W | 0.6657 | likely_pathogenic | 0.6419 | pathogenic | -1.057 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3135 | likely_benign | 0.2992 | benign | -0.776 | Destabilizing | 0.998 | D | 0.703 | prob.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.