Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26536 | 79831;79832;79833 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| N2AB | 24895 | 74908;74909;74910 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| N2A | 23968 | 72127;72128;72129 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| N2B | 17471 | 52636;52637;52638 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| Novex-1 | 17596 | 53011;53012;53013 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| Novex-2 | 17663 | 53212;53213;53214 | chr2:178566526;178566525;178566524 | chr2:179431253;179431252;179431251 |
| 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 | rs371134175  |
None | 0.003 | N | 0.306 | 0.169 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs371134175 |
None | 0.003 | N | 0.306 | 0.169 | None | gnomAD-4.0.0 | 3.84529E-06 | None | None | None | None | N | None | 3.38513E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.3936E-06 | 0 | 0 |
| I/V | None | None | None | N | 0.197 | 0.032 | 0.303781844768 | gnomAD-4.0.0 | 1.59204E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85878E-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 | 0.1323 | likely_benign | 0.141 | benign | -1.48 | Destabilizing | 0.055 | N | 0.372 | neutral | None | None | None | None | N |
| I/C | 0.4362 | ambiguous | 0.4491 | ambiguous | -0.792 | Destabilizing | 0.667 | D | 0.491 | neutral | None | None | None | None | N |
| I/D | 0.4802 | ambiguous | 0.5307 | ambiguous | -0.967 | Destabilizing | 0.667 | D | 0.565 | neutral | None | None | None | None | N |
| I/E | 0.3094 | likely_benign | 0.3653 | ambiguous | -1.007 | Destabilizing | 0.22 | N | 0.536 | neutral | None | None | None | None | N |
| I/F | 0.1256 | likely_benign | 0.1338 | benign | -1.142 | Destabilizing | 0.124 | N | 0.431 | neutral | None | None | None | None | N |
| I/G | 0.3926 | ambiguous | 0.4051 | ambiguous | -1.756 | Destabilizing | 0.22 | N | 0.5 | neutral | None | None | None | None | N |
| I/H | 0.312 | likely_benign | 0.3587 | ambiguous | -1.001 | Destabilizing | 0.883 | D | 0.494 | neutral | None | None | None | None | N |
| I/K | 0.184 | likely_benign | 0.2271 | benign | -1.003 | Destabilizing | 0.096 | N | 0.491 | neutral | N | 0.394669731 | None | None | N |
| I/L | 0.0746 | likely_benign | 0.0806 | benign | -0.817 | Destabilizing | None | N | 0.155 | neutral | N | 0.482174072 | None | None | N |
| I/M | 0.0613 | likely_benign | 0.0622 | benign | -0.568 | Destabilizing | 0.003 | N | 0.19 | neutral | N | 0.48486766 | None | None | N |
| I/N | 0.1736 | likely_benign | 0.1871 | benign | -0.726 | Destabilizing | 0.497 | N | 0.565 | neutral | None | None | None | None | N |
| I/P | 0.2702 | likely_benign | 0.268 | benign | -1.006 | Destabilizing | 0.859 | D | 0.565 | neutral | None | None | None | None | N |
| I/Q | 0.2257 | likely_benign | 0.2612 | benign | -0.964 | Destabilizing | 0.497 | N | 0.565 | neutral | None | None | None | None | N |
| I/R | 0.1364 | likely_benign | 0.166 | benign | -0.358 | Destabilizing | 0.001 | N | 0.383 | neutral | N | 0.423952488 | None | None | N |
| I/S | 0.1653 | likely_benign | 0.1758 | benign | -1.268 | Destabilizing | 0.124 | N | 0.475 | neutral | None | None | None | None | N |
| I/T | 0.0868 | likely_benign | 0.0888 | benign | -1.202 | Destabilizing | 0.003 | N | 0.306 | neutral | N | 0.42433649 | None | None | N |
| I/V | 0.0616 | likely_benign | 0.062 | benign | -1.006 | Destabilizing | None | N | 0.197 | neutral | N | 0.437055071 | None | None | N |
| I/W | 0.5449 | ambiguous | 0.5689 | pathogenic | -1.176 | Destabilizing | 0.958 | D | 0.496 | neutral | None | None | None | None | N |
| I/Y | 0.3155 | likely_benign | 0.3462 | ambiguous | -0.97 | Destabilizing | 0.667 | D | 0.557 | 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.