Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31240 | 93943;93944;93945 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| N2AB | 29599 | 89020;89021;89022 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| N2A | 28672 | 86239;86240;86241 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| N2B | 22175 | 66748;66749;66750 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| Novex-1 | 22300 | 67123;67124;67125 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| Novex-2 | 22367 | 67324;67325;67326 | chr2:178547908;178547907;178547906 | chr2:179412635;179412634;179412633 |
| 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 | rs757914126  |
-0.37 | 0.001 | D | 0.199 | 0.194 | 0.285316908763 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/G | rs757914126 |
-0.37 | 0.001 | D | 0.199 | 0.194 | 0.285316908763 | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| S/R | None | None | 0.497 | N | 0.501 | 0.299 | 0.406257615169 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 | 0.085 | likely_benign | 0.0883 | benign | -0.139 | Destabilizing | 0.072 | N | 0.395 | neutral | None | None | None | None | I |
| S/C | 0.1248 | likely_benign | 0.1229 | benign | -0.48 | Destabilizing | 0.883 | D | 0.549 | neutral | N | 0.49748407 | None | None | I |
| S/D | 0.5232 | ambiguous | 0.5455 | ambiguous | 0.083 | Stabilizing | 0.272 | N | 0.403 | neutral | None | None | None | None | I |
| S/E | 0.5426 | ambiguous | 0.5329 | ambiguous | -0.011 | Destabilizing | 0.272 | N | 0.396 | neutral | None | None | None | None | I |
| S/F | 0.1809 | likely_benign | 0.188 | benign | -0.914 | Destabilizing | 0.726 | D | 0.602 | neutral | None | None | None | None | I |
| S/G | 0.1284 | likely_benign | 0.1304 | benign | -0.185 | Destabilizing | 0.001 | N | 0.199 | neutral | D | 0.532675542 | None | None | I |
| S/H | 0.3074 | likely_benign | 0.298 | benign | -0.466 | Destabilizing | 0.968 | D | 0.527 | neutral | None | None | None | None | I |
| S/I | 0.1511 | likely_benign | 0.1593 | benign | -0.15 | Destabilizing | 0.331 | N | 0.581 | neutral | N | 0.519322243 | None | None | I |
| S/K | 0.5504 | ambiguous | 0.5318 | ambiguous | -0.354 | Destabilizing | 0.272 | N | 0.392 | neutral | None | None | None | None | I |
| S/L | 0.094 | likely_benign | 0.0923 | benign | -0.15 | Destabilizing | 0.157 | N | 0.475 | neutral | None | None | None | None | I |
| S/M | 0.1619 | likely_benign | 0.1727 | benign | -0.29 | Destabilizing | 0.909 | D | 0.527 | neutral | None | None | None | None | I |
| S/N | 0.1855 | likely_benign | 0.1939 | benign | -0.197 | Destabilizing | 0.22 | N | 0.436 | neutral | N | 0.500989562 | None | None | I |
| S/P | 0.8748 | likely_pathogenic | 0.8953 | pathogenic | -0.122 | Destabilizing | 0.726 | D | 0.496 | neutral | None | None | None | None | I |
| S/Q | 0.4377 | ambiguous | 0.4363 | ambiguous | -0.359 | Destabilizing | 0.726 | D | 0.453 | neutral | None | None | None | None | I |
| S/R | 0.4385 | ambiguous | 0.4169 | ambiguous | -0.131 | Destabilizing | 0.497 | N | 0.501 | neutral | N | 0.51574322 | None | None | I |
| S/T | 0.0666 | likely_benign | 0.0687 | benign | -0.271 | Destabilizing | None | N | 0.166 | neutral | N | 0.493154362 | None | None | I |
| S/V | 0.165 | likely_benign | 0.1788 | benign | -0.122 | Destabilizing | 0.157 | N | 0.462 | neutral | None | None | None | None | I |
| S/W | 0.298 | likely_benign | 0.2954 | benign | -1.035 | Destabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | I |
| S/Y | 0.1834 | likely_benign | 0.1802 | benign | -0.69 | Destabilizing | 0.726 | D | 0.599 | 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.