Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24234 | 72925;72926;72927 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| N2AB | 22593 | 68002;68003;68004 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| N2A | 21666 | 65221;65222;65223 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| N2B | 15169 | 45730;45731;45732 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| Novex-1 | 15294 | 46105;46106;46107 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| Novex-2 | 15361 | 46306;46307;46308 | chr2:178573432;178573431;178573430 | chr2:179438159;179438158;179438157 |
| 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 | rs939911271  |
-2.238 | 0.896 | N | 0.537 | 0.273 | 0.66819093994 | gnomAD-2.1.1 | 5.71E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.17E-05 | 0 |
| I/T | rs939911271 |
-2.238 | 0.896 | N | 0.537 | 0.273 | 0.66819093994 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs939911271 |
-2.238 | 0.896 | N | 0.537 | 0.273 | 0.66819093994 | gnomAD-4.0.0 | 2.91717E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.33615E-06 | 0 | 0 |
| I/V | rs746673481 |
-1.337 | 0.046 | N | 0.138 | 0.106 | 0.488337271218 | gnomAD-2.1.1 | 1.14E-05 | None | None | None | None | N | None | 0 | 4.95E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.17E-05 | 0 |
| I/V | rs746673481 |
-1.337 | 0.046 | N | 0.138 | 0.106 | 0.488337271218 | gnomAD-4.0.0 | 3.75198E-06 | None | None | None | None | N | None | 0 | 3.59712E-05 | None | 0 | 0 | None | 0 | 0 | 3.26203E-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 | 0.4773 | ambiguous | 0.366 | ambiguous | -1.84 | Destabilizing | 0.034 | N | 0.269 | neutral | None | None | None | None | N |
| I/C | 0.7532 | likely_pathogenic | 0.6952 | pathogenic | -1.647 | Destabilizing | 0.997 | D | 0.581 | neutral | None | None | None | None | N |
| I/D | 0.9446 | likely_pathogenic | 0.9239 | pathogenic | -2.377 | Highly Destabilizing | 0.988 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/E | 0.8546 | likely_pathogenic | 0.8173 | pathogenic | -2.359 | Highly Destabilizing | 0.976 | D | 0.644 | neutral | None | None | None | None | N |
| I/F | 0.3768 | ambiguous | 0.3107 | benign | -1.602 | Destabilizing | 0.984 | D | 0.527 | neutral | N | 0.470335735 | None | None | N |
| I/G | 0.8676 | likely_pathogenic | 0.7856 | pathogenic | -2.165 | Highly Destabilizing | 0.952 | D | 0.591 | neutral | None | None | None | None | N |
| I/H | 0.8327 | likely_pathogenic | 0.775 | pathogenic | -1.535 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/K | 0.6382 | likely_pathogenic | 0.5839 | pathogenic | -1.318 | Destabilizing | 0.976 | D | 0.65 | neutral | None | None | None | None | N |
| I/L | 0.2507 | likely_benign | 0.2065 | benign | -0.994 | Destabilizing | 0.437 | N | 0.362 | neutral | N | 0.519367023 | None | None | N |
| I/M | 0.1766 | likely_benign | 0.1522 | benign | -0.891 | Destabilizing | 0.984 | D | 0.531 | neutral | N | 0.486362849 | None | None | N |
| I/N | 0.6591 | likely_pathogenic | 0.5689 | pathogenic | -1.357 | Destabilizing | 0.984 | D | 0.692 | prob.neutral | N | 0.51226501 | None | None | N |
| I/P | 0.8579 | likely_pathogenic | 0.8221 | pathogenic | -1.249 | Destabilizing | 0.988 | D | 0.687 | prob.neutral | None | None | None | None | N |
| I/Q | 0.7262 | likely_pathogenic | 0.6601 | pathogenic | -1.589 | Destabilizing | 0.988 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/R | 0.5407 | ambiguous | 0.4812 | ambiguous | -0.757 | Destabilizing | 0.988 | D | 0.691 | prob.neutral | None | None | None | None | N |
| I/S | 0.5795 | likely_pathogenic | 0.4654 | ambiguous | -1.881 | Destabilizing | 0.811 | D | 0.531 | neutral | N | 0.506400513 | None | None | N |
| I/T | 0.38 | ambiguous | 0.3056 | benign | -1.748 | Destabilizing | 0.896 | D | 0.537 | neutral | N | 0.489006831 | None | None | N |
| I/V | 0.0685 | likely_benign | 0.0602 | benign | -1.249 | Destabilizing | 0.046 | N | 0.138 | neutral | N | 0.408753749 | None | None | N |
| I/W | 0.9322 | likely_pathogenic | 0.9178 | pathogenic | -1.766 | Destabilizing | 0.999 | D | 0.726 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7965 | likely_pathogenic | 0.7448 | pathogenic | -1.458 | Destabilizing | 0.996 | D | 0.607 | 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.