Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16761 | 50506;50507;50508 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| N2AB | 15120 | 45583;45584;45585 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| N2A | 14193 | 42802;42803;42804 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| N2B | 7696 | 23311;23312;23313 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| Novex-1 | 7821 | 23686;23687;23688 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| Novex-2 | 7888 | 23887;23888;23889 | chr2:178612130;178612129;178612128 | chr2:179476857;179476856;179476855 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.826 | N | 0.418 | 0.136 | 0.573410036937 | gnomAD-4.0.0 | 1.59561E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86446E-06 | 0 | 0 |
| V/F | None | None | 0.996 | N | 0.582 | 0.321 | 0.691532996453 | gnomAD-4.0.0 | 1.59566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86453E-06 | 0 | 0 |
| V/I | rs769565595  |
-0.311 | 0.826 | N | 0.449 | 0.207 | 0.442672919754 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| V/I | rs769565595 |
-0.311 | 0.826 | N | 0.449 | 0.207 | 0.442672919754 | gnomAD-4.0.0 | 1.59566E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86453E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1707 | likely_benign | 0.1584 | benign | -0.64 | Destabilizing | 0.826 | D | 0.418 | neutral | N | 0.480241138 | None | None | N |
| V/C | 0.7792 | likely_pathogenic | 0.7295 | pathogenic | -0.666 | Destabilizing | 0.999 | D | 0.53 | neutral | None | None | None | None | N |
| V/D | 0.4718 | ambiguous | 0.4704 | ambiguous | -0.471 | Destabilizing | 0.852 | D | 0.562 | neutral | N | 0.466432486 | None | None | N |
| V/E | 0.3353 | likely_benign | 0.3229 | benign | -0.575 | Destabilizing | 0.939 | D | 0.553 | neutral | None | None | None | None | N |
| V/F | 0.2263 | likely_benign | 0.2223 | benign | -0.766 | Destabilizing | 0.996 | D | 0.582 | neutral | N | 0.478395819 | None | None | N |
| V/G | 0.247 | likely_benign | 0.2632 | benign | -0.8 | Destabilizing | 0.92 | D | 0.539 | neutral | N | 0.476626858 | None | None | N |
| V/H | 0.6282 | likely_pathogenic | 0.5926 | pathogenic | -0.32 | Destabilizing | 0.991 | D | 0.617 | neutral | None | None | None | None | N |
| V/I | 0.09 | likely_benign | 0.0812 | benign | -0.361 | Destabilizing | 0.826 | D | 0.449 | neutral | N | 0.470327086 | None | None | N |
| V/K | 0.425 | ambiguous | 0.4179 | ambiguous | -0.618 | Destabilizing | 0.939 | D | 0.567 | neutral | None | None | None | None | N |
| V/L | 0.2183 | likely_benign | 0.1866 | benign | -0.361 | Destabilizing | 0.826 | D | 0.448 | neutral | N | 0.458663326 | None | None | N |
| V/M | 0.1383 | likely_benign | 0.124 | benign | -0.38 | Destabilizing | 0.997 | D | 0.48 | neutral | None | None | None | None | N |
| V/N | 0.2904 | likely_benign | 0.2797 | benign | -0.35 | Destabilizing | 0.079 | N | 0.407 | neutral | None | None | None | None | N |
| V/P | 0.8947 | likely_pathogenic | 0.8901 | pathogenic | -0.419 | Destabilizing | 0.997 | D | 0.617 | neutral | None | None | None | None | N |
| V/Q | 0.349 | ambiguous | 0.3375 | benign | -0.599 | Destabilizing | 0.991 | D | 0.634 | neutral | None | None | None | None | N |
| V/R | 0.3891 | ambiguous | 0.3944 | ambiguous | -0.052 | Destabilizing | 0.991 | D | 0.619 | neutral | None | None | None | None | N |
| V/S | 0.2005 | likely_benign | 0.2001 | benign | -0.722 | Destabilizing | 0.759 | D | 0.513 | neutral | None | None | None | None | N |
| V/T | 0.1311 | likely_benign | 0.1178 | benign | -0.724 | Destabilizing | 0.079 | N | 0.143 | neutral | None | None | None | None | N |
| V/W | 0.857 | likely_pathogenic | 0.8452 | pathogenic | -0.848 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/Y | 0.6814 | likely_pathogenic | 0.6488 | pathogenic | -0.561 | Destabilizing | 0.997 | D | 0.577 | 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.