Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22216 | 66871;66872;66873 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| N2AB | 20575 | 61948;61949;61950 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| N2A | 19648 | 59167;59168;59169 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| N2B | 13151 | 39676;39677;39678 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| Novex-1 | 13276 | 40051;40052;40053 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| Novex-2 | 13343 | 40252;40253;40254 | chr2:178581622;178581621;178581620 | chr2:179446349;179446348;179446347 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs1365775589  |
-0.645 | 0.999 | N | 0.473 | 0.268 | 0.60829468558 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 8.91E-06 | 0 |
| R/C | rs1365775589 |
-0.645 | 0.999 | N | 0.473 | 0.268 | 0.60829468558 | gnomAD-4.0.0 | 8.90043E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.29913E-06 | 6.95894E-05 | 0 |
| R/H | None | -1.062 | 0.031 | N | 0.247 | 0.155 | None | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | I | None | 1.29349E-04 | 0 | None | 0 | 5.64E-05 | None | 0 | None | 0 | 3.56E-05 | 0 |
| R/H | None | -1.062 | 0.031 | N | 0.247 | 0.155 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 1.31182E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | None | -1.062 | 0.031 | N | 0.247 | 0.155 | None | gnomAD-4.0.0 | 4.46481E-05 | None | None | None | None | I | None | 9.35329E-05 | 3.33778E-05 | None | 0 | 4.47928E-05 | None | 0 | 0 | 4.91851E-05 | 0 | 4.80893E-05 |
| R/L | rs753717922 |
None | 0.653 | N | 0.414 | 0.225 | 0.441017621159 | gnomAD-4.0.0 | 2.7386E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59952E-06 | 0 | 0 |
| R/P | rs753717922 |
-0.088 | 0.902 | N | 0.506 | 0.291 | 0.364141725642 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| R/P | rs753717922 |
-0.088 | 0.902 | N | 0.506 | 0.291 | 0.364141725642 | gnomAD-4.0.0 | 6.8465E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99881E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3896 | ambiguous | 0.3625 | ambiguous | -0.631 | Destabilizing | 0.495 | N | 0.373 | neutral | None | None | None | None | I |
| R/C | 0.1752 | likely_benign | 0.1697 | benign | -0.81 | Destabilizing | 0.999 | D | 0.473 | neutral | N | 0.473409927 | None | None | I |
| R/D | 0.6531 | likely_pathogenic | 0.6295 | pathogenic | -0.054 | Destabilizing | 0.329 | N | 0.411 | neutral | None | None | None | None | I |
| R/E | 0.3555 | ambiguous | 0.3344 | benign | 0.096 | Stabilizing | 0.176 | N | 0.28 | neutral | None | None | None | None | I |
| R/F | 0.5325 | ambiguous | 0.5209 | ambiguous | -0.454 | Destabilizing | 0.944 | D | 0.486 | neutral | None | None | None | None | I |
| R/G | 0.388 | ambiguous | 0.3476 | ambiguous | -0.917 | Destabilizing | 0.485 | N | 0.397 | neutral | N | 0.5112089 | None | None | I |
| R/H | 0.0883 | likely_benign | 0.091 | benign | -1.171 | Destabilizing | 0.031 | N | 0.247 | neutral | N | 0.444754621 | None | None | I |
| R/I | 0.2518 | likely_benign | 0.2431 | benign | 0.136 | Stabilizing | 0.944 | D | 0.539 | neutral | None | None | None | None | I |
| R/K | 0.121 | likely_benign | 0.1102 | benign | -0.43 | Destabilizing | 0.004 | N | 0.176 | neutral | None | None | None | None | I |
| R/L | 0.2965 | likely_benign | 0.2919 | benign | 0.136 | Stabilizing | 0.653 | D | 0.414 | neutral | N | 0.504821645 | None | None | I |
| R/M | 0.3054 | likely_benign | 0.2769 | benign | -0.472 | Destabilizing | 0.981 | D | 0.484 | neutral | None | None | None | None | I |
| R/N | 0.4772 | ambiguous | 0.4483 | ambiguous | -0.393 | Destabilizing | 0.003 | N | 0.235 | neutral | None | None | None | None | I |
| R/P | 0.9557 | likely_pathogenic | 0.9495 | pathogenic | -0.1 | Destabilizing | 0.902 | D | 0.506 | neutral | N | 0.507880593 | None | None | I |
| R/Q | 0.1064 | likely_benign | 0.0993 | benign | -0.385 | Destabilizing | 0.031 | N | 0.233 | neutral | None | None | None | None | I |
| R/S | 0.3947 | ambiguous | 0.3642 | ambiguous | -1.017 | Destabilizing | 0.485 | N | 0.376 | neutral | N | 0.394899017 | None | None | I |
| R/T | 0.1906 | likely_benign | 0.1722 | benign | -0.678 | Destabilizing | 0.495 | N | 0.382 | neutral | None | None | None | None | I |
| R/V | 0.2959 | likely_benign | 0.2853 | benign | -0.1 | Destabilizing | 0.828 | D | 0.492 | neutral | None | None | None | None | I |
| R/W | 0.2749 | likely_benign | 0.268 | benign | -0.266 | Destabilizing | 0.995 | D | 0.481 | neutral | None | None | None | None | I |
| R/Y | 0.3752 | ambiguous | 0.3742 | ambiguous | 0.032 | Stabilizing | 0.704 | D | 0.561 | 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.