Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19903 | 59932;59933;59934 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| N2AB | 18262 | 55009;55010;55011 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| N2A | 17335 | 52228;52229;52230 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| N2B | 10838 | 32737;32738;32739 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| Novex-1 | 10963 | 33112;33113;33114 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| Novex-2 | 11030 | 33313;33314;33315 | chr2:178592197;178592196;178592195 | chr2:179456924;179456923;179456922 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs2154185463  |
None | 1.0 | N | 0.403 | 0.283 | 0.364926071151 | gnomAD-4.0.0 | 1.59464E-06 | None | None | None | None | I | None | 0 | 2.29337E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs374163882 |
-0.003 | 1.0 | N | 0.591 | 0.453 | None | gnomAD-2.1.1 | 2.17E-05 | None | None | None | None | I | None | 2.49917E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs374163882 |
-0.003 | 1.0 | N | 0.591 | 0.453 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 1.93022E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/H | rs374163882 |
-0.003 | 1.0 | N | 0.591 | 0.453 | None | gnomAD-4.0.0 | 8.06444E-06 | None | None | None | None | I | None | 1.73602E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs374163882 |
None | 1.0 | N | 0.623 | 0.383 | 0.343788945184 | gnomAD-4.0.0 | 3.42472E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.7001E-06 | 0 | 3.31763E-05 |
| D/V | None | None | 1.0 | N | 0.706 | 0.593 | 0.605567239383 | gnomAD-4.0.0 | 2.73975E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60013E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3216 | likely_benign | 0.3239 | benign | -0.277 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.483343747 | None | None | I |
| D/C | 0.7077 | likely_pathogenic | 0.6955 | pathogenic | 0.092 | Stabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/E | 0.2782 | likely_benign | 0.2632 | benign | -0.309 | Destabilizing | 1.0 | D | 0.403 | neutral | N | 0.474113808 | None | None | I |
| D/F | 0.6137 | likely_pathogenic | 0.6381 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.645 | neutral | None | None | None | None | I |
| D/G | 0.3642 | ambiguous | 0.3625 | ambiguous | -0.479 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.503271654 | None | None | I |
| D/H | 0.374 | ambiguous | 0.3834 | ambiguous | -0.192 | Destabilizing | 1.0 | D | 0.591 | neutral | N | 0.480394459 | None | None | I |
| D/I | 0.4637 | ambiguous | 0.4657 | ambiguous | 0.207 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | I |
| D/K | 0.6117 | likely_pathogenic | 0.6141 | pathogenic | 0.297 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/L | 0.4553 | ambiguous | 0.4653 | ambiguous | 0.207 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| D/M | 0.7036 | likely_pathogenic | 0.6954 | pathogenic | 0.398 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| D/N | 0.1259 | likely_benign | 0.1214 | benign | 0.012 | Stabilizing | 1.0 | D | 0.623 | neutral | N | 0.504568142 | None | None | I |
| D/P | 0.9188 | likely_pathogenic | 0.9291 | pathogenic | 0.068 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/Q | 0.4899 | ambiguous | 0.4889 | ambiguous | 0.057 | Stabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | I |
| D/R | 0.589 | likely_pathogenic | 0.6058 | pathogenic | 0.403 | Stabilizing | 1.0 | D | 0.675 | neutral | None | None | None | None | I |
| D/S | 0.2169 | likely_benign | 0.2155 | benign | -0.089 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| D/T | 0.3629 | ambiguous | 0.3634 | ambiguous | 0.07 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/V | 0.2999 | likely_benign | 0.2981 | benign | 0.068 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.493547963 | None | None | I |
| D/W | 0.885 | likely_pathogenic | 0.8958 | pathogenic | -0.137 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| D/Y | 0.2692 | likely_benign | 0.2963 | benign | -0.021 | Destabilizing | 1.0 | D | 0.627 | neutral | N | 0.508840598 | 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.