Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35450 | 106573;106574;106575 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| N2AB | 33809 | 101650;101651;101652 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| N2A | 32882 | 98869;98870;98871 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| N2B | 26385 | 79378;79379;79380 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| Novex-1 | 26510 | 79753;79754;79755 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| Novex-2 | 26577 | 79954;79955;79956 | chr2:178530267;178530266;178530265 | chr2:179394994;179394993;179394992 |
| 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/I | rs371022420  |
None | 0.863 | N | 0.596 | 0.139 | 0.347879110917 | gnomAD-4.0.0 | 1.37635E-06 | None | None | None | None | N | None | 0 | 4.56892E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs371022420 |
-0.73 | 0.029 | N | 0.179 | 0.117 | 0.104622674875 | gnomAD-2.1.1 | 6.14E-05 | None | None | None | None | N | None | 3.73196E-04 | 2.02324E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.42613E-04 |
| T/S | rs371022420 |
-0.73 | 0.029 | N | 0.179 | 0.117 | 0.104622674875 | gnomAD-3.1.2 | 1.6423E-04 | None | None | None | None | N | None | 5.78787E-04 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs371022420 |
-0.73 | 0.029 | N | 0.179 | 0.117 | 0.104622674875 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/S | rs371022420 |
-0.73 | 0.029 | N | 0.179 | 0.117 | 0.104622674875 | gnomAD-4.0.0 | 3.48809E-05 | None | None | None | None | N | None | 5.7616E-04 | 2.03114E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.61041E-05 |
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 | 0.086 | likely_benign | 0.0848 | benign | -0.719 | Destabilizing | 0.002 | N | 0.178 | neutral | N | 0.476974188 | None | None | N |
| T/C | 0.5863 | likely_pathogenic | 0.6038 | pathogenic | -0.496 | Destabilizing | 0.985 | D | 0.612 | neutral | None | None | None | None | N |
| T/D | 0.2919 | likely_benign | 0.2961 | benign | -0.042 | Destabilizing | 0.705 | D | 0.524 | neutral | None | None | None | None | N |
| T/E | 0.2082 | likely_benign | 0.2044 | benign | 0.001 | Stabilizing | 0.705 | D | 0.509 | neutral | None | None | None | None | N |
| T/F | 0.2127 | likely_benign | 0.2222 | benign | -0.78 | Destabilizing | 0.944 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/G | 0.2803 | likely_benign | 0.2822 | benign | -0.994 | Destabilizing | 0.33 | N | 0.558 | neutral | None | None | None | None | N |
| T/H | 0.286 | likely_benign | 0.2917 | benign | -1.087 | Destabilizing | 0.995 | D | 0.673 | neutral | None | None | None | None | N |
| T/I | 0.1308 | likely_benign | 0.1326 | benign | -0.073 | Destabilizing | 0.863 | D | 0.596 | neutral | N | 0.492212999 | None | None | N |
| T/K | 0.1779 | likely_benign | 0.1784 | benign | -0.539 | Destabilizing | 0.705 | D | 0.521 | neutral | None | None | None | None | N |
| T/L | 0.1069 | likely_benign | 0.1086 | benign | -0.073 | Destabilizing | 0.544 | D | 0.516 | neutral | None | None | None | None | N |
| T/M | 0.1063 | likely_benign | 0.1112 | benign | -0.121 | Destabilizing | 0.995 | D | 0.623 | neutral | None | None | None | None | N |
| T/N | 0.13 | likely_benign | 0.1285 | benign | -0.641 | Destabilizing | 0.643 | D | 0.488 | neutral | N | 0.480379852 | None | None | N |
| T/P | 0.3071 | likely_benign | 0.334 | benign | -0.256 | Destabilizing | 0.928 | D | 0.602 | neutral | N | 0.506825686 | None | None | N |
| T/Q | 0.2161 | likely_benign | 0.217 | benign | -0.649 | Destabilizing | 0.944 | D | 0.639 | neutral | None | None | None | None | N |
| T/R | 0.1556 | likely_benign | 0.1618 | benign | -0.379 | Destabilizing | 0.944 | D | 0.607 | neutral | None | None | None | None | N |
| T/S | 0.112 | likely_benign | 0.111 | benign | -0.916 | Destabilizing | 0.029 | N | 0.179 | neutral | N | 0.442762827 | None | None | N |
| T/V | 0.1125 | likely_benign | 0.1105 | benign | -0.256 | Destabilizing | 0.544 | D | 0.479 | neutral | None | None | None | None | N |
| T/W | 0.6073 | likely_pathogenic | 0.6445 | pathogenic | -0.81 | Destabilizing | 0.995 | D | 0.718 | prob.delet. | None | None | None | None | N |
| T/Y | 0.305 | likely_benign | 0.3124 | benign | -0.519 | Destabilizing | 0.981 | D | 0.692 | prob.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.