Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32370 | 97333;97334;97335 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| N2AB | 30729 | 92410;92411;92412 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| N2A | 29802 | 89629;89630;89631 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| N2B | 23305 | 70138;70139;70140 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| Novex-1 | 23430 | 70513;70514;70515 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| Novex-2 | 23497 | 70714;70715;70716 | chr2:178542746;178542745;178542744 | chr2:179407473;179407472;179407471 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs146098114  |
-0.267 | 1.0 | N | 0.779 | 0.298 | None | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.33927E-04 | None | 0 | None | 0 | 0 | 0 |
| T/N | rs146098114 |
-0.267 | 1.0 | N | 0.779 | 0.298 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 5.77812E-04 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs146098114 |
-0.267 | 1.0 | N | 0.779 | 0.298 | None | gnomAD-4.0.0 | 2.56184E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.84919E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0989 | likely_benign | 0.0932 | benign | -0.803 | Destabilizing | 0.999 | D | 0.557 | neutral | N | 0.482490006 | None | None | I |
| T/C | 0.4438 | ambiguous | 0.4089 | ambiguous | -0.458 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| T/D | 0.3443 | ambiguous | 0.3399 | benign | -0.317 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| T/E | 0.3864 | ambiguous | 0.3665 | ambiguous | -0.353 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| T/F | 0.4737 | ambiguous | 0.4252 | ambiguous | -1.09 | Destabilizing | 1.0 | D | 0.773 | deleterious | None | None | None | None | I |
| T/G | 0.1974 | likely_benign | 0.1894 | benign | -1.006 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| T/H | 0.3586 | ambiguous | 0.3258 | benign | -1.381 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| T/I | 0.3469 | ambiguous | 0.2938 | benign | -0.364 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.491012382 | None | None | I |
| T/K | 0.3225 | likely_benign | 0.2957 | benign | -0.679 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | I |
| T/L | 0.1748 | likely_benign | 0.1531 | benign | -0.364 | Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| T/M | 0.1321 | likely_benign | 0.1181 | benign | 0.093 | Stabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| T/N | 0.1153 | likely_benign | 0.1134 | benign | -0.541 | Destabilizing | 1.0 | D | 0.779 | deleterious | N | 0.47941706 | None | None | I |
| T/P | 0.5779 | likely_pathogenic | 0.581 | pathogenic | -0.481 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | N | 0.513978482 | None | None | I |
| T/Q | 0.2876 | likely_benign | 0.2693 | benign | -0.827 | Destabilizing | 1.0 | D | 0.758 | deleterious | None | None | None | None | I |
| T/R | 0.3045 | likely_benign | 0.2708 | benign | -0.384 | Destabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | I |
| T/S | 0.0984 | likely_benign | 0.0985 | benign | -0.805 | Destabilizing | 0.999 | D | 0.561 | neutral | N | 0.504294075 | None | None | I |
| T/V | 0.1975 | likely_benign | 0.1706 | benign | -0.481 | Destabilizing | 0.999 | D | 0.639 | neutral | None | None | None | None | I |
| T/W | 0.8091 | likely_pathogenic | 0.7833 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| T/Y | 0.5205 | ambiguous | 0.4872 | ambiguous | -0.76 | Destabilizing | 1.0 | D | 0.766 | deleterious | 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.