Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16430 | 49513;49514;49515 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| N2AB | 14789 | 44590;44591;44592 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| N2A | 13862 | 41809;41810;41811 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| N2B | 7365 | 22318;22319;22320 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| Novex-1 | 7490 | 22693;22694;22695 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| Novex-2 | 7557 | 22894;22895;22896 | chr2:178614109;178614108;178614107 | chr2:179478836;179478835;179478834 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.969 | N | 0.35 | 0.27 | 0.633181949713 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/L | None | None | 0.48 | N | 0.289 | 0.208 | 0.444706120422 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| M/T | rs973490041  |
0.631 | 0.912 | N | 0.443 | 0.245 | 0.666668332583 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| M/T | rs973490041 |
0.631 | 0.912 | N | 0.443 | 0.245 | 0.666668332583 | gnomAD-4.0.0 | 4.06086E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.82029E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3262 | likely_benign | 0.2786 | benign | -0.312 | Destabilizing | 0.737 | D | 0.451 | neutral | None | None | None | None | I |
| M/C | 0.7586 | likely_pathogenic | 0.6781 | pathogenic | -0.427 | Destabilizing | 0.998 | D | 0.416 | neutral | None | None | None | None | I |
| M/D | 0.8627 | likely_pathogenic | 0.7957 | pathogenic | 0.594 | Stabilizing | 0.872 | D | 0.546 | neutral | None | None | None | None | I |
| M/E | 0.525 | ambiguous | 0.4262 | ambiguous | 0.548 | Stabilizing | 0.584 | D | 0.513 | neutral | None | None | None | None | I |
| M/F | 0.5523 | ambiguous | 0.5032 | ambiguous | -0.027 | Destabilizing | 0.993 | D | 0.342 | neutral | None | None | None | None | I |
| M/G | 0.6597 | likely_pathogenic | 0.5765 | pathogenic | -0.468 | Destabilizing | 0.932 | D | 0.532 | neutral | None | None | None | None | I |
| M/H | 0.548 | ambiguous | 0.478 | ambiguous | 0.363 | Stabilizing | 0.98 | D | 0.493 | neutral | None | None | None | None | I |
| M/I | 0.3422 | ambiguous | 0.2916 | benign | 0.002 | Stabilizing | 0.969 | D | 0.35 | neutral | N | 0.438096916 | None | None | I |
| M/K | 0.1943 | likely_benign | 0.151 | benign | 0.561 | Stabilizing | 0.514 | D | 0.445 | neutral | N | 0.337993333 | None | None | I |
| M/L | 0.1405 | likely_benign | 0.1402 | benign | 0.002 | Stabilizing | 0.48 | N | 0.289 | neutral | N | 0.44511267 | None | None | I |
| M/N | 0.4986 | ambiguous | 0.4231 | ambiguous | 0.625 | Stabilizing | 0.932 | D | 0.536 | neutral | None | None | None | None | I |
| M/P | 0.7278 | likely_pathogenic | 0.6557 | pathogenic | -0.075 | Destabilizing | 0.977 | D | 0.499 | neutral | None | None | None | None | I |
| M/Q | 0.1933 | likely_benign | 0.1565 | benign | 0.503 | Stabilizing | 0.1 | N | 0.095 | neutral | None | None | None | None | I |
| M/R | 0.2327 | likely_benign | 0.1908 | benign | 0.997 | Stabilizing | 0.837 | D | 0.458 | neutral | N | 0.409386891 | None | None | I |
| M/S | 0.3991 | ambiguous | 0.34 | ambiguous | 0.149 | Stabilizing | 0.737 | D | 0.44 | neutral | None | None | None | None | I |
| M/T | 0.1848 | likely_benign | 0.1572 | benign | 0.21 | Stabilizing | 0.912 | D | 0.443 | neutral | N | 0.45289017 | None | None | I |
| M/V | 0.0921 | likely_benign | 0.0801 | benign | -0.075 | Destabilizing | 0.811 | D | 0.352 | neutral | N | 0.447221797 | None | None | I |
| M/W | 0.8161 | likely_pathogenic | 0.7854 | pathogenic | -0.028 | Destabilizing | 0.998 | D | 0.429 | neutral | None | None | None | None | I |
| M/Y | 0.7001 | likely_pathogenic | 0.6325 | pathogenic | 0.151 | Stabilizing | 0.993 | D | 0.447 | 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.