Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28580 | 85963;85964;85965 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| N2AB | 26939 | 81040;81041;81042 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| N2A | 26012 | 78259;78260;78261 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| N2B | 19515 | 58768;58769;58770 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| Novex-1 | 19640 | 59143;59144;59145 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| Novex-2 | 19707 | 59344;59345;59346 | chr2:178560394;178560393;178560392 | chr2:179425121;179425120;179425119 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs759326015  |
-0.908 | 0.489 | N | 0.607 | 0.229 | 0.227934060464 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| S/G | rs759326015 |
-0.908 | 0.489 | N | 0.607 | 0.229 | 0.227934060464 | gnomAD-4.0.0 | 3.18298E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71654E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1538 | likely_benign | 0.1411 | benign | -0.535 | Destabilizing | 0.717 | D | 0.645 | neutral | None | None | None | None | I |
| S/C | 0.0939 | likely_benign | 0.0878 | benign | -0.288 | Destabilizing | 0.997 | D | 0.63 | neutral | N | 0.489160779 | None | None | I |
| S/D | 0.6051 | likely_pathogenic | 0.4753 | ambiguous | -0.419 | Destabilizing | 0.754 | D | 0.621 | neutral | None | None | None | None | I |
| S/E | 0.7429 | likely_pathogenic | 0.6692 | pathogenic | -0.505 | Destabilizing | 0.86 | D | 0.643 | neutral | None | None | None | None | I |
| S/F | 0.5499 | ambiguous | 0.4821 | ambiguous | -1.119 | Destabilizing | 0.993 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/G | 0.1649 | likely_benign | 0.1424 | benign | -0.664 | Destabilizing | 0.489 | N | 0.607 | neutral | N | 0.472299702 | None | None | I |
| S/H | 0.3919 | ambiguous | 0.3012 | benign | -1.273 | Destabilizing | 0.956 | D | 0.607 | neutral | None | None | None | None | I |
| S/I | 0.4139 | ambiguous | 0.3355 | benign | -0.318 | Destabilizing | 0.971 | D | 0.69 | prob.neutral | N | 0.50533925 | None | None | I |
| S/K | 0.7377 | likely_pathogenic | 0.648 | pathogenic | -0.611 | Destabilizing | 0.754 | D | 0.643 | neutral | None | None | None | None | I |
| S/L | 0.2214 | likely_benign | 0.1992 | benign | -0.318 | Destabilizing | 0.978 | D | 0.666 | neutral | None | None | None | None | I |
| S/M | 0.3114 | likely_benign | 0.2794 | benign | 0.196 | Stabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | I |
| S/N | 0.115 | likely_benign | 0.097 | benign | -0.383 | Destabilizing | 0.006 | N | 0.401 | neutral | N | 0.489703757 | None | None | I |
| S/P | 0.9666 | likely_pathogenic | 0.947 | pathogenic | -0.362 | Destabilizing | 0.978 | D | 0.621 | neutral | None | None | None | None | I |
| S/Q | 0.5864 | likely_pathogenic | 0.5034 | ambiguous | -0.733 | Destabilizing | 0.956 | D | 0.672 | neutral | None | None | None | None | I |
| S/R | 0.6434 | likely_pathogenic | 0.5615 | ambiguous | -0.338 | Destabilizing | 0.942 | D | 0.623 | neutral | N | 0.503311334 | None | None | I |
| S/T | 0.1628 | likely_benign | 0.1447 | benign | -0.446 | Destabilizing | 0.822 | D | 0.624 | neutral | N | 0.485006496 | None | None | I |
| S/V | 0.3703 | ambiguous | 0.3178 | benign | -0.362 | Destabilizing | 0.978 | D | 0.688 | prob.neutral | None | None | None | None | I |
| S/W | 0.6405 | likely_pathogenic | 0.5733 | pathogenic | -1.088 | Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | I |
| S/Y | 0.3741 | ambiguous | 0.3113 | benign | -0.821 | Destabilizing | 0.993 | D | 0.697 | prob.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.