Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21572 | 64939;64940;64941 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| N2AB | 19931 | 60016;60017;60018 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| N2A | 19004 | 57235;57236;57237 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| N2B | 12507 | 37744;37745;37746 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| Novex-1 | 12632 | 38119;38120;38121 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| Novex-2 | 12699 | 38320;38321;38322 | chr2:178584927;178584926;178584925 | chr2:179449654;179449653;179449652 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs765749707  |
-0.365 | 0.684 | N | 0.347 | 0.322 | 0.58940213094 | gnomAD-2.1.1 | 1.79E-05 | None | None | None | None | I | None | 1.24605E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| I/T | rs765749707 |
-0.365 | 0.684 | N | 0.347 | 0.322 | 0.58940213094 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs765749707 |
-0.365 | 0.684 | N | 0.347 | 0.322 | 0.58940213094 | gnomAD-4.0.0 | 9.91821E-06 | None | None | None | None | I | None | 6.67592E-05 | 3.335E-05 | None | 0 | 0 | None | 0 | 0 | 5.93455E-06 | 0 | 3.20287E-05 |
| I/V | None | None | 0.012 | N | 0.115 | 0.081 | 0.258779203287 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9375E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2268 | likely_benign | 0.2275 | benign | -1.655 | Destabilizing | 0.543 | D | 0.379 | neutral | None | None | None | None | I |
| I/C | 0.6679 | likely_pathogenic | 0.6412 | pathogenic | -1.206 | Destabilizing | 0.996 | D | 0.345 | neutral | None | None | None | None | I |
| I/D | 0.823 | likely_pathogenic | 0.8389 | pathogenic | -1.541 | Destabilizing | 0.91 | D | 0.429 | neutral | None | None | None | None | I |
| I/E | 0.6345 | likely_pathogenic | 0.656 | pathogenic | -1.563 | Destabilizing | 0.59 | D | 0.388 | neutral | None | None | None | None | I |
| I/F | 0.2909 | likely_benign | 0.2882 | benign | -1.523 | Destabilizing | 0.91 | D | 0.386 | neutral | None | None | None | None | I |
| I/G | 0.6949 | likely_pathogenic | 0.6948 | pathogenic | -1.942 | Destabilizing | 0.854 | D | 0.402 | neutral | None | None | None | None | I |
| I/H | 0.6436 | likely_pathogenic | 0.6703 | pathogenic | -1.237 | Destabilizing | 0.987 | D | 0.364 | neutral | None | None | None | None | I |
| I/K | 0.3567 | ambiguous | 0.387 | ambiguous | -0.976 | Destabilizing | 0.521 | D | 0.385 | neutral | N | 0.517809585 | None | None | I |
| I/L | 0.1716 | likely_benign | 0.1628 | benign | -0.941 | Destabilizing | 0.001 | N | 0.067 | neutral | N | 0.481656784 | None | None | I |
| I/M | 0.1174 | likely_benign | 0.1156 | benign | -0.669 | Destabilizing | 0.884 | D | 0.42 | neutral | N | 0.478133642 | None | None | I |
| I/N | 0.4752 | ambiguous | 0.4772 | ambiguous | -0.834 | Destabilizing | 0.953 | D | 0.431 | neutral | None | None | None | None | I |
| I/P | 0.6699 | likely_pathogenic | 0.7108 | pathogenic | -1.15 | Destabilizing | 0.984 | D | 0.429 | neutral | None | None | None | None | I |
| I/Q | 0.5011 | ambiguous | 0.5218 | ambiguous | -1.109 | Destabilizing | 0.101 | N | 0.323 | neutral | None | None | None | None | I |
| I/R | 0.2825 | likely_benign | 0.3247 | benign | -0.384 | Destabilizing | 0.884 | D | 0.433 | neutral | N | 0.468561309 | None | None | I |
| I/S | 0.343 | ambiguous | 0.3496 | ambiguous | -1.415 | Destabilizing | 0.742 | D | 0.353 | neutral | None | None | None | None | I |
| I/T | 0.1013 | likely_benign | 0.1019 | benign | -1.325 | Destabilizing | 0.684 | D | 0.347 | neutral | N | 0.518905663 | None | None | I |
| I/V | 0.0678 | likely_benign | 0.0634 | benign | -1.15 | Destabilizing | 0.012 | N | 0.115 | neutral | N | 0.393939012 | None | None | I |
| I/W | 0.8498 | likely_pathogenic | 0.8701 | pathogenic | -1.58 | Destabilizing | 0.996 | D | 0.409 | neutral | None | None | None | None | I |
| I/Y | 0.6975 | likely_pathogenic | 0.7089 | pathogenic | -1.3 | Destabilizing | 0.953 | D | 0.423 | 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.