Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24988 | 75187;75188;75189 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| N2AB | 23347 | 70264;70265;70266 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| N2A | 22420 | 67483;67484;67485 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| N2B | 15923 | 47992;47993;47994 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| Novex-1 | 16048 | 48367;48368;48369 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| Novex-2 | 16115 | 48568;48569;48570 | chr2:178571170;178571169;178571168 | chr2:179435897;179435896;179435895 |
| 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/M | rs777883873  |
None | 0.987 | N | 0.475 | 0.21 | 0.270889551736 | gnomAD-4.0.0 | 2.73742E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59831E-06 | 0 | 0 |
| I/T | None | None | 0.967 | N | 0.515 | 0.323 | 0.652561814978 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85928E-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 | 0.3107 | likely_benign | 0.3219 | benign | -0.528 | Destabilizing | 0.916 | D | 0.581 | neutral | None | None | None | None | I |
| I/C | 0.8029 | likely_pathogenic | 0.8058 | pathogenic | -0.792 | Destabilizing | 0.999 | D | 0.549 | neutral | None | None | None | None | I |
| I/D | 0.8758 | likely_pathogenic | 0.8833 | pathogenic | -0.085 | Destabilizing | 0.996 | D | 0.64 | neutral | None | None | None | None | I |
| I/E | 0.7892 | likely_pathogenic | 0.7953 | pathogenic | -0.174 | Destabilizing | 0.987 | D | 0.638 | neutral | None | None | None | None | I |
| I/F | 0.3516 | ambiguous | 0.36 | ambiguous | -0.56 | Destabilizing | 0.967 | D | 0.488 | neutral | N | 0.501879302 | None | None | I |
| I/G | 0.8101 | likely_pathogenic | 0.8226 | pathogenic | -0.664 | Destabilizing | 0.987 | D | 0.64 | neutral | None | None | None | None | I |
| I/H | 0.768 | likely_pathogenic | 0.7787 | pathogenic | 0.049 | Stabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | I |
| I/K | 0.62 | likely_pathogenic | 0.6341 | pathogenic | -0.328 | Destabilizing | 0.987 | D | 0.639 | neutral | None | None | None | None | I |
| I/L | 0.143 | likely_benign | 0.1427 | benign | -0.293 | Destabilizing | 0.011 | N | 0.237 | neutral | N | 0.476248177 | None | None | I |
| I/M | 0.1138 | likely_benign | 0.1216 | benign | -0.472 | Destabilizing | 0.987 | D | 0.475 | neutral | N | 0.475882818 | None | None | I |
| I/N | 0.5691 | likely_pathogenic | 0.6001 | pathogenic | -0.224 | Destabilizing | 0.994 | D | 0.647 | neutral | N | 0.514361061 | None | None | I |
| I/P | 0.8004 | likely_pathogenic | 0.7866 | pathogenic | -0.339 | Destabilizing | 0.996 | D | 0.648 | neutral | None | None | None | None | I |
| I/Q | 0.6791 | likely_pathogenic | 0.6937 | pathogenic | -0.412 | Destabilizing | 0.996 | D | 0.646 | neutral | None | None | None | None | I |
| I/R | 0.4891 | ambiguous | 0.499 | ambiguous | 0.184 | Stabilizing | 0.987 | D | 0.648 | neutral | None | None | None | None | I |
| I/S | 0.4283 | ambiguous | 0.446 | ambiguous | -0.667 | Destabilizing | 0.983 | D | 0.554 | neutral | N | 0.465433751 | None | None | I |
| I/T | 0.2981 | likely_benign | 0.3183 | benign | -0.647 | Destabilizing | 0.967 | D | 0.515 | neutral | N | 0.503431992 | None | None | I |
| I/V | 0.1001 | likely_benign | 0.104 | benign | -0.339 | Destabilizing | 0.426 | N | 0.401 | neutral | N | 0.492889711 | None | None | I |
| I/W | 0.8897 | likely_pathogenic | 0.8936 | pathogenic | -0.573 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| I/Y | 0.7339 | likely_pathogenic | 0.7386 | pathogenic | -0.332 | Destabilizing | 0.987 | D | 0.53 | 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.