Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27017 | 81274;81275;81276 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| N2AB | 25376 | 76351;76352;76353 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| N2A | 24449 | 73570;73571;73572 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| N2B | 17952 | 54079;54080;54081 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| Novex-1 | 18077 | 54454;54455;54456 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| Novex-2 | 18144 | 54655;54656;54657 | chr2:178565083;178565082;178565081 | chr2:179429810;179429809;179429808 |
| 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 | rs993539436  |
-0.8 | 0.174 | N | 0.358 | 0.112 | 0.20549828249 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs993539436 |
-0.8 | 0.174 | N | 0.358 | 0.112 | 0.20549828249 | gnomAD-4.0.0 | 1.59167E-06 | None | None | None | None | N | None | 0 | 2.28666E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1216 | likely_benign | 0.0992 | benign | -0.458 | Destabilizing | 0.174 | N | 0.358 | neutral | N | 0.506205725 | None | None | N |
| T/C | 0.705 | likely_pathogenic | 0.5513 | ambiguous | -0.107 | Destabilizing | 0.973 | D | 0.383 | neutral | None | None | None | None | N |
| T/D | 0.6855 | likely_pathogenic | 0.5814 | pathogenic | -0.249 | Destabilizing | 0.575 | D | 0.316 | neutral | None | None | None | None | N |
| T/E | 0.6061 | likely_pathogenic | 0.5462 | ambiguous | -0.338 | Destabilizing | 0.404 | N | 0.338 | neutral | None | None | None | None | N |
| T/F | 0.7133 | likely_pathogenic | 0.575 | pathogenic | -1.031 | Destabilizing | 0.906 | D | 0.448 | neutral | None | None | None | None | N |
| T/G | 0.2873 | likely_benign | 0.2049 | benign | -0.572 | Destabilizing | 0.004 | N | 0.282 | neutral | None | None | None | None | N |
| T/H | 0.5859 | likely_pathogenic | 0.4574 | ambiguous | -1.006 | Destabilizing | 0.973 | D | 0.453 | neutral | None | None | None | None | N |
| T/I | 0.6457 | likely_pathogenic | 0.5242 | ambiguous | -0.273 | Destabilizing | 0.782 | D | 0.333 | neutral | N | 0.492982213 | None | None | N |
| T/K | 0.4941 | ambiguous | 0.4335 | ambiguous | -0.366 | Destabilizing | 0.004 | N | 0.236 | neutral | None | None | None | None | N |
| T/L | 0.2632 | likely_benign | 0.1902 | benign | -0.273 | Destabilizing | 0.575 | D | 0.334 | neutral | None | None | None | None | N |
| T/M | 0.1808 | likely_benign | 0.1434 | benign | 0.221 | Stabilizing | 0.991 | D | 0.347 | neutral | None | None | None | None | N |
| T/N | 0.2306 | likely_benign | 0.177 | benign | -0.121 | Destabilizing | 0.338 | N | 0.302 | neutral | N | 0.468077102 | None | None | N |
| T/P | 0.8551 | likely_pathogenic | 0.7876 | pathogenic | -0.308 | Destabilizing | 0.782 | D | 0.333 | neutral | N | 0.478739072 | None | None | N |
| T/Q | 0.4373 | ambiguous | 0.3648 | ambiguous | -0.472 | Destabilizing | 0.826 | D | 0.331 | neutral | None | None | None | None | N |
| T/R | 0.4918 | ambiguous | 0.4237 | ambiguous | -0.035 | Destabilizing | 0.704 | D | 0.315 | neutral | None | None | None | None | N |
| T/S | 0.1274 | likely_benign | 0.0928 | benign | -0.288 | Destabilizing | 0.003 | N | 0.21 | neutral | N | 0.408849749 | None | None | N |
| T/V | 0.4 | ambiguous | 0.314 | benign | -0.308 | Destabilizing | 0.575 | D | 0.303 | neutral | None | None | None | None | N |
| T/W | 0.9371 | likely_pathogenic | 0.8665 | pathogenic | -1.007 | Destabilizing | 0.991 | D | 0.559 | neutral | None | None | None | None | N |
| T/Y | 0.7133 | likely_pathogenic | 0.5596 | ambiguous | -0.729 | Destabilizing | 0.906 | D | 0.441 | 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.