Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19397 | 58414;58415;58416 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| N2AB | 17756 | 53491;53492;53493 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| N2A | 16829 | 50710;50711;50712 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| N2B | 10332 | 31219;31220;31221 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| Novex-1 | 10457 | 31594;31595;31596 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| Novex-2 | 10524 | 31795;31796;31797 | chr2:178594204;178594203;178594202 | chr2:179458931;179458930;179458929 |
| 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/M | rs373527448  |
-0.062 | 0.005 | N | 0.191 | 0.066 | None | gnomAD-2.1.1 | 8.23E-05 | None | None | None | None | I | None | 4.13E-05 | 4.82352E-04 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 4.22297E-04 |
| T/M | rs373527448 |
-0.062 | 0.005 | N | 0.191 | 0.066 | None | gnomAD-3.1.2 | 1.381E-04 | None | None | None | None | I | None | 1.20639E-04 | 7.86473E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 4.79846E-04 |
| T/M | rs373527448 |
-0.062 | 0.005 | N | 0.191 | 0.066 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/M | rs373527448 |
-0.062 | 0.005 | N | 0.191 | 0.066 | None | gnomAD-4.0.0 | 3.96696E-05 | None | None | None | None | I | None | 7.99701E-05 | 6.33883E-04 | None | 0 | 2.23814E-05 | None | 0 | 0 | 1.2716E-05 | 1.0981E-05 | 4.80354E-05 |
| T/P | None | None | 0.266 | N | 0.387 | 0.328 | 0.52463718601 | gnomAD-4.0.0 | 2.0417E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.1012E-05 | 6.07755E-05 | 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 | 0.1259 | likely_benign | 0.1183 | benign | -0.418 | Destabilizing | 0.01 | N | 0.167 | neutral | N | 0.50769974 | None | None | I |
| T/C | 0.4698 | ambiguous | 0.4353 | ambiguous | -0.36 | Destabilizing | 0.628 | D | 0.294 | neutral | None | None | None | None | I |
| T/D | 0.4864 | ambiguous | 0.4332 | ambiguous | 0.303 | Stabilizing | 0.136 | N | 0.373 | neutral | None | None | None | None | I |
| T/E | 0.4047 | ambiguous | 0.3638 | ambiguous | 0.274 | Stabilizing | 0.136 | N | 0.314 | neutral | None | None | None | None | I |
| T/F | 0.3204 | likely_benign | 0.2503 | benign | -0.69 | Destabilizing | 0.072 | N | 0.413 | neutral | None | None | None | None | I |
| T/G | 0.4374 | ambiguous | 0.4167 | ambiguous | -0.617 | Destabilizing | 0.136 | N | 0.362 | neutral | None | None | None | None | I |
| T/H | 0.3583 | ambiguous | 0.3087 | benign | -0.816 | Destabilizing | 0.628 | D | 0.288 | neutral | None | None | None | None | I |
| T/I | 0.1328 | likely_benign | 0.1062 | benign | None | Stabilizing | None | N | 0.141 | neutral | None | None | None | None | I |
| T/K | 0.4269 | ambiguous | 0.3443 | ambiguous | -0.414 | Destabilizing | 0.232 | N | 0.321 | neutral | N | 0.482668009 | None | None | I |
| T/L | 0.1122 | likely_benign | 0.0981 | benign | None | Stabilizing | 0.001 | N | 0.211 | neutral | None | None | None | None | I |
| T/M | 0.0931 | likely_benign | 0.0868 | benign | -0.002 | Destabilizing | 0.005 | N | 0.191 | neutral | N | 0.48680718 | None | None | I |
| T/N | 0.1378 | likely_benign | 0.1321 | benign | -0.304 | Destabilizing | 0.325 | N | 0.249 | neutral | None | None | None | None | I |
| T/P | 0.2885 | likely_benign | 0.2407 | benign | -0.108 | Destabilizing | 0.266 | N | 0.387 | neutral | N | 0.520477036 | None | None | I |
| T/Q | 0.3191 | likely_benign | 0.2943 | benign | -0.431 | Destabilizing | 0.356 | N | 0.355 | neutral | None | None | None | None | I |
| T/R | 0.3694 | ambiguous | 0.274 | benign | -0.19 | Destabilizing | 0.515 | D | 0.375 | neutral | N | 0.485671029 | None | None | I |
| T/S | 0.1497 | likely_benign | 0.1451 | benign | -0.565 | Destabilizing | 0.047 | N | 0.19 | neutral | N | 0.481649289 | None | None | I |
| T/V | 0.1244 | likely_benign | 0.1077 | benign | -0.108 | Destabilizing | None | N | 0.144 | neutral | None | None | None | None | I |
| T/W | 0.6711 | likely_pathogenic | 0.5823 | pathogenic | -0.698 | Destabilizing | 0.864 | D | 0.293 | neutral | None | None | None | None | I |
| T/Y | 0.3405 | ambiguous | 0.2841 | benign | -0.417 | Destabilizing | 0.356 | N | 0.379 | 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.