Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19276 | 58051;58052;58053 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| N2AB | 17635 | 53128;53129;53130 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| N2A | 16708 | 50347;50348;50349 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| N2B | 10211 | 30856;30857;30858 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| Novex-1 | 10336 | 31231;31232;31233 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| Novex-2 | 10403 | 31432;31433;31434 | chr2:178595528;178595527;178595526 | chr2:179460255;179460254;179460253 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs756493505  |
-1.365 | 0.808 | N | 0.535 | 0.107 | 0.43046518545 | gnomAD-2.1.1 | 1.98E-05 | None | None | None | None | N | None | 5.42E-05 | 3.75E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.38E-05 | 0 |
| L/F | rs756493505 |
-1.365 | 0.808 | N | 0.535 | 0.107 | 0.43046518545 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 4.87E-05 | 6.6E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/F | rs756493505 |
-1.365 | 0.808 | N | 0.535 | 0.107 | 0.43046518545 | gnomAD-4.0.0 | 5.77486E-06 | None | None | None | None | N | None | 2.73373E-05 | 3.85446E-05 | None | 0 | 0 | None | 0 | 0 | 4.34527E-06 | 0 | 0 |
| L/P | rs748582312 |
-1.201 | 0.963 | N | 0.795 | 0.375 | 0.798364575988 | gnomAD-2.1.1 | 5.85E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.45E-05 | 0 |
| L/P | rs748582312 |
-1.201 | 0.963 | N | 0.795 | 0.375 | 0.798364575988 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| L/P | rs748582312 |
-1.201 | 0.963 | N | 0.795 | 0.375 | 0.798364575988 | gnomAD-4.0.0 | 1.9236E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.73788E-06 | 0 | 1.65328E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2391 | likely_benign | 0.285 | benign | -1.692 | Destabilizing | 0.397 | N | 0.607 | neutral | None | None | None | None | N |
| L/C | 0.4354 | ambiguous | 0.4871 | ambiguous | -1.143 | Destabilizing | 0.992 | D | 0.651 | prob.neutral | None | None | None | None | N |
| L/D | 0.7919 | likely_pathogenic | 0.8674 | pathogenic | -1.048 | Destabilizing | 0.972 | D | 0.795 | deleterious | None | None | None | None | N |
| L/E | 0.416 | ambiguous | 0.5028 | ambiguous | -0.948 | Destabilizing | 0.972 | D | 0.781 | deleterious | None | None | None | None | N |
| L/F | 0.1397 | likely_benign | 0.1798 | benign | -0.922 | Destabilizing | 0.808 | D | 0.535 | neutral | N | 0.450829658 | None | None | N |
| L/G | 0.669 | likely_pathogenic | 0.7533 | pathogenic | -2.085 | Highly Destabilizing | 0.919 | D | 0.765 | deleterious | None | None | None | None | N |
| L/H | 0.291 | likely_benign | 0.3516 | ambiguous | -1.074 | Destabilizing | 0.99 | D | 0.803 | deleterious | N | 0.50370135 | None | None | N |
| L/I | 0.062 | likely_benign | 0.068 | benign | -0.64 | Destabilizing | 0.002 | N | 0.199 | neutral | N | 0.349588015 | None | None | N |
| L/K | 0.3366 | likely_benign | 0.3751 | ambiguous | -1.149 | Destabilizing | 0.919 | D | 0.707 | prob.delet. | None | None | None | None | N |
| L/M | 0.0903 | likely_benign | 0.09 | benign | -0.704 | Destabilizing | 0.848 | D | 0.581 | neutral | None | None | None | None | N |
| L/N | 0.4906 | ambiguous | 0.5858 | pathogenic | -1.199 | Destabilizing | 0.972 | D | 0.793 | deleterious | None | None | None | None | N |
| L/P | 0.8159 | likely_pathogenic | 0.8967 | pathogenic | -0.964 | Destabilizing | 0.963 | D | 0.795 | deleterious | N | 0.503874709 | None | None | N |
| L/Q | 0.2195 | likely_benign | 0.2366 | benign | -1.208 | Destabilizing | 0.972 | D | 0.746 | deleterious | None | None | None | None | N |
| L/R | 0.2751 | likely_benign | 0.3355 | benign | -0.718 | Destabilizing | 0.963 | D | 0.739 | deleterious | N | 0.483208648 | None | None | N |
| L/S | 0.3616 | ambiguous | 0.4396 | ambiguous | -1.88 | Destabilizing | 0.919 | D | 0.701 | prob.delet. | None | None | None | None | N |
| L/T | 0.1647 | likely_benign | 0.1949 | benign | -1.638 | Destabilizing | 0.615 | D | 0.651 | prob.neutral | None | None | None | None | N |
| L/V | 0.0628 | likely_benign | 0.0651 | benign | -0.964 | Destabilizing | 0.007 | N | 0.247 | neutral | N | 0.333079767 | None | None | N |
| L/W | 0.3343 | likely_benign | 0.4276 | ambiguous | -1.011 | Destabilizing | 0.992 | D | 0.734 | deleterious | None | None | None | None | N |
| L/Y | 0.3984 | ambiguous | 0.475 | ambiguous | -0.777 | Destabilizing | 0.919 | D | 0.655 | 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.