Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3432 | 10519;10520;10521 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| N2AB | 3432 | 10519;10520;10521 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| N2A | 3432 | 10519;10520;10521 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| N2B | 3386 | 10381;10382;10383 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| Novex-1 | 3386 | 10381;10382;10383 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| Novex-2 | 3386 | 10381;10382;10383 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
| Novex-3 | 3432 | 10519;10520;10521 | chr2:178758993;178758992;178758991 | chr2:179623720;179623719;179623718 |
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/N | rs1392831001  |
-0.202 | None | N | 0.071 | 0.115 | 0.146414634003 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| S/N | rs1392831001 |
-0.202 | None | N | 0.071 | 0.115 | 0.146414634003 | gnomAD-4.0.0 | 4.7724E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71409E-06 | 0 | 3.02243E-05 |
| S/T | rs1392831001 |
None | None | N | 0.073 | 0.087 | 0.117506650769 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs1392831001 |
None | None | N | 0.073 | 0.087 | 0.117506650769 | gnomAD-4.0.0 | 6.5716E-06 | None | None | None | None | N | None | 2.41301E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0986 | likely_benign | 0.0912 | benign | -0.646 | Destabilizing | 0.004 | N | 0.251 | neutral | None | None | None | None | N |
| S/C | 0.0773 | likely_benign | 0.0526 | benign | -0.423 | Destabilizing | 0.427 | N | 0.4 | neutral | D | 0.531820374 | None | None | N |
| S/D | 0.2689 | likely_benign | 0.2446 | benign | -0.079 | Destabilizing | 0.009 | N | 0.267 | neutral | None | None | None | None | N |
| S/E | 0.2032 | likely_benign | 0.1808 | benign | -0.111 | Destabilizing | 0.004 | N | 0.233 | neutral | None | None | None | None | N |
| S/F | 0.1558 | likely_benign | 0.132 | benign | -0.917 | Destabilizing | 0.044 | N | 0.518 | neutral | None | None | None | None | N |
| S/G | 0.1007 | likely_benign | 0.0758 | benign | -0.862 | Destabilizing | 0.006 | N | 0.233 | neutral | N | 0.5129643 | None | None | N |
| S/H | 0.0656 | likely_benign | 0.0479 | benign | -1.369 | Destabilizing | 0.245 | N | 0.421 | neutral | None | None | None | None | N |
| S/I | 0.0838 | likely_benign | 0.073 | benign | -0.185 | Destabilizing | None | N | 0.203 | neutral | N | 0.468039108 | None | None | N |
| S/K | 0.1129 | likely_benign | 0.0832 | benign | -0.634 | Destabilizing | None | N | 0.083 | neutral | None | None | None | None | N |
| S/L | 0.0887 | likely_benign | 0.0785 | benign | -0.185 | Destabilizing | 0.004 | N | 0.327 | neutral | None | None | None | None | N |
| S/M | 0.1424 | likely_benign | 0.1141 | benign | 0.12 | Stabilizing | 0.138 | N | 0.418 | neutral | None | None | None | None | N |
| S/N | 0.0978 | likely_benign | 0.0975 | benign | -0.492 | Destabilizing | None | N | 0.071 | neutral | N | 0.460924054 | None | None | N |
| S/P | 0.7061 | likely_pathogenic | 0.7115 | pathogenic | -0.306 | Destabilizing | 0.085 | N | 0.451 | neutral | None | None | None | None | N |
| S/Q | 0.108 | likely_benign | 0.0784 | benign | -0.701 | Destabilizing | 0.009 | N | 0.265 | neutral | None | None | None | None | N |
| S/R | 0.0739 | likely_benign | 0.0476 | benign | -0.496 | Destabilizing | None | N | 0.131 | neutral | N | 0.48436784 | None | None | N |
| S/T | 0.0699 | likely_benign | 0.0645 | benign | -0.562 | Destabilizing | None | N | 0.073 | neutral | N | 0.384970764 | None | None | N |
| S/V | 0.1283 | likely_benign | 0.1116 | benign | -0.306 | Destabilizing | 0.004 | N | 0.335 | neutral | None | None | None | None | N |
| S/W | 0.1669 | likely_benign | 0.1178 | benign | -0.87 | Destabilizing | 0.788 | D | 0.479 | neutral | None | None | None | None | N |
| S/Y | 0.1072 | likely_benign | 0.0877 | benign | -0.613 | Destabilizing | 0.085 | N | 0.509 | 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.