Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22238 | 66937;66938;66939 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| N2AB | 20597 | 62014;62015;62016 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| N2A | 19670 | 59233;59234;59235 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| N2B | 13173 | 39742;39743;39744 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| Novex-1 | 13298 | 40117;40118;40119 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| Novex-2 | 13365 | 40318;40319;40320 | chr2:178581556;178581555;178581554 | chr2:179446283;179446282;179446281 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs1233016025  |
None | 0.99 | N | 0.741 | 0.419 | 0.821136106345 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/N | rs1233016025 |
None | 0.99 | N | 0.741 | 0.419 | 0.821136106345 | gnomAD-4.0.0 | 2.56756E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79743E-06 | 0 | 0 |
| I/T | rs1233016025 |
-0.476 | 0.822 | N | 0.617 | 0.327 | 0.554998169399 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| I/T | rs1233016025 |
-0.476 | 0.822 | N | 0.617 | 0.327 | 0.554998169399 | gnomAD-4.0.0 | 1.59521E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86605E-06 | 0 | 0 |
| I/V | None | None | 0.006 | N | 0.228 | 0.069 | 0.232513804876 | 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 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2024 | likely_benign | 0.2098 | benign | -0.638 | Destabilizing | 0.754 | D | 0.54 | neutral | None | None | None | None | I |
| I/C | 0.6357 | likely_pathogenic | 0.6566 | pathogenic | -0.695 | Destabilizing | 0.994 | D | 0.629 | neutral | None | None | None | None | I |
| I/D | 0.865 | likely_pathogenic | 0.8499 | pathogenic | -0.205 | Destabilizing | 0.993 | D | 0.738 | prob.delet. | None | None | None | None | I |
| I/E | 0.7207 | likely_pathogenic | 0.7111 | pathogenic | -0.301 | Destabilizing | 0.978 | D | 0.743 | deleterious | None | None | None | None | I |
| I/F | 0.306 | likely_benign | 0.2828 | benign | -0.656 | Destabilizing | 0.942 | D | 0.616 | neutral | N | 0.489140117 | None | None | I |
| I/G | 0.7839 | likely_pathogenic | 0.7745 | pathogenic | -0.789 | Destabilizing | 0.978 | D | 0.737 | prob.delet. | None | None | None | None | I |
| I/H | 0.7566 | likely_pathogenic | 0.7254 | pathogenic | -0.006 | Destabilizing | 0.998 | D | 0.752 | deleterious | None | None | None | None | I |
| I/K | 0.693 | likely_pathogenic | 0.6743 | pathogenic | -0.347 | Destabilizing | 0.978 | D | 0.741 | deleterious | None | None | None | None | I |
| I/L | 0.1975 | likely_benign | 0.186 | benign | -0.365 | Destabilizing | 0.294 | N | 0.353 | neutral | N | 0.475152099 | None | None | I |
| I/M | 0.13 | likely_benign | 0.1274 | benign | -0.435 | Destabilizing | 0.942 | D | 0.612 | neutral | D | 0.522367256 | None | None | I |
| I/N | 0.4391 | ambiguous | 0.4511 | ambiguous | -0.18 | Destabilizing | 0.99 | D | 0.741 | deleterious | N | 0.469189511 | None | None | I |
| I/P | 0.925 | likely_pathogenic | 0.9161 | pathogenic | -0.424 | Destabilizing | 0.993 | D | 0.747 | deleterious | None | None | None | None | I |
| I/Q | 0.6629 | likely_pathogenic | 0.6403 | pathogenic | -0.417 | Destabilizing | 0.993 | D | 0.741 | deleterious | None | None | None | None | I |
| I/R | 0.5739 | likely_pathogenic | 0.5618 | ambiguous | 0.243 | Stabilizing | 0.978 | D | 0.742 | deleterious | None | None | None | None | I |
| I/S | 0.3536 | ambiguous | 0.3569 | ambiguous | -0.634 | Destabilizing | 0.942 | D | 0.688 | prob.neutral | N | 0.501471909 | None | None | I |
| I/T | 0.1491 | likely_benign | 0.1509 | benign | -0.621 | Destabilizing | 0.822 | D | 0.617 | neutral | N | 0.469949979 | None | None | I |
| I/V | 0.0953 | likely_benign | 0.0889 | benign | -0.424 | Destabilizing | 0.006 | N | 0.228 | neutral | N | 0.405444085 | None | None | I |
| I/W | 0.8721 | likely_pathogenic | 0.8538 | pathogenic | -0.647 | Destabilizing | 0.998 | D | 0.772 | deleterious | None | None | None | None | I |
| I/Y | 0.6946 | likely_pathogenic | 0.6838 | pathogenic | -0.406 | Destabilizing | 0.978 | D | 0.627 | 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.