Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30142 | 90649;90650;90651 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| N2AB | 28501 | 85726;85727;85728 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| N2A | 27574 | 82945;82946;82947 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| N2B | 21077 | 63454;63455;63456 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| Novex-1 | 21202 | 63829;63830;63831 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| Novex-2 | 21269 | 64030;64031;64032 | chr2:178552476;178552475;178552474 | chr2:179417203;179417202;179417201 |
| 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/A | None | None | None | N | 0.111 | 0.105 | 0.247322355667 | gnomAD-4.0.0 | 2.05658E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.32083E-05 | 1.66052E-05 |
| T/I | rs754759596  |
None | 0.055 | N | 0.35 | 0.124 | 0.401327265625 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/I | rs754759596 |
None | 0.055 | N | 0.35 | 0.124 | 0.401327265625 | gnomAD-4.0.0 | 6.57125E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46972E-05 | 0 | 0 |
| T/N | None | None | 0.029 | N | 0.197 | 0.08 | 0.377274123778 | gnomAD-4.0.0 | 6.85568E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01349E-07 | 0 | 0 |
| T/S | rs754759596 |
-0.098 | None | N | 0.119 | 0.11 | 0.230578612272 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| T/S | rs754759596 |
-0.098 | None | N | 0.119 | 0.11 | 0.230578612272 | gnomAD-4.0.0 | 6.85568E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16047E-05 | 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 | 0.0682 | likely_benign | 0.0704 | benign | -0.132 | Destabilizing | None | N | 0.111 | neutral | N | 0.4699895 | None | None | I |
| T/C | 0.3457 | ambiguous | 0.3398 | benign | -0.424 | Destabilizing | 0.356 | N | 0.314 | neutral | None | None | None | None | I |
| T/D | 0.4704 | ambiguous | 0.4988 | ambiguous | 0.14 | Stabilizing | 0.038 | N | 0.305 | neutral | None | None | None | None | I |
| T/E | 0.383 | ambiguous | 0.4194 | ambiguous | 0.066 | Stabilizing | 0.016 | N | 0.305 | neutral | None | None | None | None | I |
| T/F | 0.2722 | likely_benign | 0.2558 | benign | -0.73 | Destabilizing | 0.356 | N | 0.344 | neutral | None | None | None | None | I |
| T/G | 0.2388 | likely_benign | 0.2304 | benign | -0.226 | Destabilizing | 0.016 | N | 0.249 | neutral | None | None | None | None | I |
| T/H | 0.264 | likely_benign | 0.2814 | benign | -0.366 | Destabilizing | 0.356 | N | 0.321 | neutral | None | None | None | None | I |
| T/I | 0.1596 | likely_benign | 0.1617 | benign | -0.011 | Destabilizing | 0.055 | N | 0.35 | neutral | N | 0.454945477 | None | None | I |
| T/K | 0.2803 | likely_benign | 0.3351 | benign | -0.277 | Destabilizing | None | N | 0.201 | neutral | None | None | None | None | I |
| T/L | 0.1083 | likely_benign | 0.1116 | benign | -0.011 | Destabilizing | 0.016 | N | 0.29 | neutral | None | None | None | None | I |
| T/M | 0.0888 | likely_benign | 0.0903 | benign | -0.178 | Destabilizing | 0.356 | N | 0.309 | neutral | None | None | None | None | I |
| T/N | 0.1218 | likely_benign | 0.1192 | benign | -0.181 | Destabilizing | 0.029 | N | 0.197 | neutral | N | 0.489615411 | None | None | I |
| T/P | 0.1066 | likely_benign | 0.1367 | benign | -0.025 | Destabilizing | None | N | 0.198 | neutral | N | 0.496381206 | None | None | I |
| T/Q | 0.2492 | likely_benign | 0.277 | benign | -0.34 | Destabilizing | 0.038 | N | 0.397 | neutral | None | None | None | None | I |
| T/R | 0.248 | likely_benign | 0.3046 | benign | 0.003 | Stabilizing | 0.038 | N | 0.348 | neutral | None | None | None | None | I |
| T/S | 0.1024 | likely_benign | 0.0924 | benign | -0.336 | Destabilizing | None | N | 0.119 | neutral | N | 0.44393905 | None | None | I |
| T/V | 0.1241 | likely_benign | 0.1203 | benign | -0.025 | Destabilizing | 0.016 | N | 0.222 | neutral | None | None | None | None | I |
| T/W | 0.5865 | likely_pathogenic | 0.5935 | pathogenic | -0.829 | Destabilizing | 0.864 | D | 0.325 | neutral | None | None | None | None | I |
| T/Y | 0.2979 | likely_benign | 0.2737 | benign | -0.494 | Destabilizing | 0.356 | N | 0.321 | 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.