Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26829 | 80710;80711;80712 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| N2AB | 25188 | 75787;75788;75789 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| N2A | 24261 | 73006;73007;73008 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| N2B | 17764 | 53515;53516;53517 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| Novex-1 | 17889 | 53890;53891;53892 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| Novex-2 | 17956 | 54091;54092;54093 | chr2:178565647;178565646;178565645 | chr2:179430374;179430373;179430372 |
| 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 | rs1705511518  |
None | None | N | 0.173 | 0.15 | 0.119812018005 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1705511518 |
None | None | N | 0.173 | 0.15 | 0.119812018005 | gnomAD-4.0.0 | 5.57819E-06 | None | None | None | None | N | None | 1.33561E-05 | 1.66733E-05 | None | 0 | 0 | None | 0 | 0 | 5.93412E-06 | 0 | 0 |
| I/V | rs781744126 |
-0.414 | None | N | 0.104 | 0.08 | 0.112648838833 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs781744126 |
-0.414 | None | N | 0.104 | 0.08 | 0.112648838833 | gnomAD-4.0.0 | 4.77477E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57756E-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 | 0.1006 | likely_benign | 0.0889 | benign | -1.09 | Destabilizing | 0.003 | N | 0.234 | neutral | None | None | None | None | N |
| I/C | 0.4314 | ambiguous | 0.3943 | ambiguous | -0.69 | Destabilizing | 0.356 | N | 0.437 | neutral | None | None | None | None | N |
| I/D | 0.3138 | likely_benign | 0.2747 | benign | -0.569 | Destabilizing | 0.072 | N | 0.491 | neutral | None | None | None | None | N |
| I/E | 0.2489 | likely_benign | 0.2371 | benign | -0.638 | Destabilizing | 0.072 | N | 0.447 | neutral | None | None | None | None | N |
| I/F | 0.124 | likely_benign | 0.107 | benign | -0.91 | Destabilizing | 0.055 | N | 0.271 | neutral | N | 0.447600138 | None | None | N |
| I/G | 0.2894 | likely_benign | 0.2509 | benign | -1.314 | Destabilizing | 0.031 | N | 0.419 | neutral | None | None | None | None | N |
| I/H | 0.2717 | likely_benign | 0.2427 | benign | -0.514 | Destabilizing | 0.628 | D | 0.456 | neutral | None | None | None | None | N |
| I/K | 0.1848 | likely_benign | 0.1738 | benign | -0.689 | Destabilizing | 0.072 | N | 0.451 | neutral | None | None | None | None | N |
| I/L | 0.0848 | likely_benign | 0.0813 | benign | -0.596 | Destabilizing | None | N | 0.114 | neutral | N | 0.402443852 | None | None | N |
| I/M | 0.0725 | likely_benign | 0.07 | benign | -0.478 | Destabilizing | 0.171 | N | 0.365 | neutral | N | 0.454160751 | None | None | N |
| I/N | 0.1284 | likely_benign | 0.1107 | benign | -0.446 | Destabilizing | 0.055 | N | 0.519 | neutral | N | 0.429147664 | None | None | N |
| I/P | 0.248 | likely_benign | 0.2088 | benign | -0.727 | Destabilizing | 0.136 | N | 0.519 | neutral | None | None | None | None | N |
| I/Q | 0.2171 | likely_benign | 0.2051 | benign | -0.694 | Destabilizing | 0.356 | N | 0.546 | neutral | None | None | None | None | N |
| I/R | 0.1498 | likely_benign | 0.1401 | benign | -0.045 | Destabilizing | 0.072 | N | 0.537 | neutral | None | None | None | None | N |
| I/S | 0.1155 | likely_benign | 0.1046 | benign | -0.949 | Destabilizing | 0.012 | N | 0.331 | neutral | N | 0.409521753 | None | None | N |
| I/T | 0.0718 | likely_benign | 0.0702 | benign | -0.91 | Destabilizing | None | N | 0.173 | neutral | N | 0.381508432 | None | None | N |
| I/V | 0.0501 | likely_benign | 0.0508 | benign | -0.727 | Destabilizing | None | N | 0.104 | neutral | N | 0.380489712 | None | None | N |
| I/W | 0.5971 | likely_pathogenic | 0.5421 | ambiguous | -0.917 | Destabilizing | 0.864 | D | 0.456 | neutral | None | None | None | None | N |
| I/Y | 0.331 | likely_benign | 0.2997 | benign | -0.694 | Destabilizing | 0.136 | N | 0.485 | 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.