Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15714 | 47365;47366;47367 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| N2AB | 14073 | 42442;42443;42444 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| N2A | 13146 | 39661;39662;39663 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| N2B | 6649 | 20170;20171;20172 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| Novex-1 | 6774 | 20545;20546;20547 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| Novex-2 | 6841 | 20746;20747;20748 | chr2:178618318;178618317;178618316 | chr2:179483045;179483044;179483043 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | rs750388617  |
-1.22 | 0.996 | N | 0.553 | 0.39 | 0.631375494303 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| C/F | rs750388617 |
-1.22 | 0.996 | N | 0.553 | 0.39 | 0.631375494303 | gnomAD-4.0.0 | 6.84605E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65837E-05 |
| C/S | None | None | 0.704 | N | 0.415 | 0.193 | 0.520161069619 | gnomAD-4.0.0 | 6.84605E-07 | None | None | None | None | N | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.3468 | ambiguous | 0.3399 | benign | -1.793 | Destabilizing | 0.733 | D | 0.301 | neutral | None | None | None | None | N |
| C/D | 0.6911 | likely_pathogenic | 0.719 | pathogenic | -0.448 | Destabilizing | 0.969 | D | 0.534 | neutral | None | None | None | None | N |
| C/E | 0.7284 | likely_pathogenic | 0.7453 | pathogenic | -0.301 | Destabilizing | 0.969 | D | 0.541 | neutral | None | None | None | None | N |
| C/F | 0.4373 | ambiguous | 0.4866 | ambiguous | -1.147 | Destabilizing | 0.996 | D | 0.553 | neutral | N | 0.471593625 | None | None | N |
| C/G | 0.1496 | likely_benign | 0.1723 | benign | -2.117 | Highly Destabilizing | 0.959 | D | 0.505 | neutral | N | 0.453362206 | None | None | N |
| C/H | 0.5465 | ambiguous | 0.5486 | ambiguous | -1.913 | Destabilizing | 0.999 | D | 0.568 | neutral | None | None | None | None | N |
| C/I | 0.7266 | likely_pathogenic | 0.7758 | pathogenic | -0.94 | Destabilizing | 0.939 | D | 0.473 | neutral | None | None | None | None | N |
| C/K | 0.5978 | likely_pathogenic | 0.6311 | pathogenic | -0.879 | Destabilizing | 0.939 | D | 0.533 | neutral | None | None | None | None | N |
| C/L | 0.4179 | ambiguous | 0.4887 | ambiguous | -0.94 | Destabilizing | 0.863 | D | 0.413 | neutral | None | None | None | None | N |
| C/M | 0.6279 | likely_pathogenic | 0.6708 | pathogenic | 0.108 | Stabilizing | 0.997 | D | 0.526 | neutral | None | None | None | None | N |
| C/N | 0.4339 | ambiguous | 0.3887 | ambiguous | -1.145 | Destabilizing | 0.991 | D | 0.586 | neutral | None | None | None | None | N |
| C/P | 0.4698 | ambiguous | 0.39 | ambiguous | -1.2 | Destabilizing | 0.02 | N | 0.491 | neutral | None | None | None | None | N |
| C/Q | 0.5087 | ambiguous | 0.5253 | ambiguous | -0.916 | Destabilizing | 0.997 | D | 0.57 | neutral | None | None | None | None | N |
| C/R | 0.2777 | likely_benign | 0.324 | benign | -0.815 | Destabilizing | 0.988 | D | 0.575 | neutral | N | 0.463888867 | None | None | N |
| C/S | 0.285 | likely_benign | 0.2845 | benign | -1.668 | Destabilizing | 0.704 | D | 0.415 | neutral | N | 0.452773271 | None | None | N |
| C/T | 0.34 | likely_benign | 0.3436 | ambiguous | -1.325 | Destabilizing | 0.079 | N | 0.269 | neutral | None | None | None | None | N |
| C/V | 0.5444 | ambiguous | 0.5785 | pathogenic | -1.2 | Destabilizing | 0.863 | D | 0.413 | neutral | None | None | None | None | N |
| C/W | 0.6632 | likely_pathogenic | 0.7245 | pathogenic | -1.174 | Destabilizing | 0.999 | D | 0.569 | neutral | D | 0.564172059 | None | None | N |
| C/Y | 0.4963 | ambiguous | 0.5316 | ambiguous | -1.144 | Destabilizing | 0.996 | D | 0.56 | neutral | N | 0.451660565 | 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.