Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17888 | 53887;53888;53889 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| N2AB | 16247 | 48964;48965;48966 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| N2A | 15320 | 46183;46184;46185 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| N2B | 8823 | 26692;26693;26694 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| Novex-1 | 8948 | 27067;27068;27069 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| Novex-2 | 9015 | 27268;27269;27270 | chr2:178605633;178605632;178605631 | chr2:179470360;179470359;179470358 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs778009539  |
-0.161 | None | N | 0.069 | 0.074 | 0.0611884634855 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/N | rs778009539 |
-0.161 | None | N | 0.069 | 0.074 | 0.0611884634855 | gnomAD-4.0.0 | 1.61001E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43802E-05 | 0 |
| S/R | None | None | 0.317 | N | 0.395 | 0.164 | 0.18274738541 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1607 | likely_benign | 0.1531 | benign | -0.44 | Destabilizing | 0.035 | N | 0.385 | neutral | None | None | None | None | I |
| S/C | 0.1467 | likely_benign | 0.1374 | benign | -0.269 | Destabilizing | 0.78 | D | 0.371 | neutral | N | 0.501431836 | None | None | I |
| S/D | 0.6498 | likely_pathogenic | 0.5764 | pathogenic | 0.076 | Stabilizing | 0.081 | N | 0.294 | neutral | None | None | None | None | I |
| S/E | 0.7979 | likely_pathogenic | 0.7565 | pathogenic | -0.022 | Destabilizing | 0.081 | N | 0.319 | neutral | None | None | None | None | I |
| S/F | 0.3567 | ambiguous | 0.313 | benign | -1.074 | Destabilizing | 0.555 | D | 0.491 | neutral | None | None | None | None | I |
| S/G | 0.1607 | likely_benign | 0.141 | benign | -0.54 | Destabilizing | 0.027 | N | 0.345 | neutral | N | 0.4777469 | None | None | I |
| S/H | 0.402 | ambiguous | 0.3523 | ambiguous | -1.087 | Destabilizing | 0.38 | N | 0.363 | neutral | None | None | None | None | I |
| S/I | 0.3924 | ambiguous | 0.3547 | ambiguous | -0.305 | Destabilizing | 0.188 | N | 0.486 | neutral | N | 0.497506097 | None | None | I |
| S/K | 0.9054 | likely_pathogenic | 0.8739 | pathogenic | -0.48 | Destabilizing | 0.081 | N | 0.318 | neutral | None | None | None | None | I |
| S/L | 0.2584 | likely_benign | 0.2381 | benign | -0.305 | Destabilizing | 0.081 | N | 0.436 | neutral | None | None | None | None | I |
| S/M | 0.311 | likely_benign | 0.2907 | benign | 0.046 | Stabilizing | 0.824 | D | 0.35 | neutral | None | None | None | None | I |
| S/N | 0.1151 | likely_benign | 0.1014 | benign | -0.211 | Destabilizing | None | N | 0.069 | neutral | N | 0.410175114 | None | None | I |
| S/P | 0.9622 | likely_pathogenic | 0.9441 | pathogenic | -0.322 | Destabilizing | 0.555 | D | 0.375 | neutral | None | None | None | None | I |
| S/Q | 0.6362 | likely_pathogenic | 0.6097 | pathogenic | -0.489 | Destabilizing | 0.38 | N | 0.358 | neutral | None | None | None | None | I |
| S/R | 0.8637 | likely_pathogenic | 0.8335 | pathogenic | -0.272 | Destabilizing | 0.317 | N | 0.395 | neutral | N | 0.450925658 | None | None | I |
| S/T | 0.1333 | likely_benign | 0.1178 | benign | -0.325 | Destabilizing | None | N | 0.093 | neutral | N | 0.463220165 | None | None | I |
| S/V | 0.3753 | ambiguous | 0.3324 | benign | -0.322 | Destabilizing | 0.081 | N | 0.475 | neutral | None | None | None | None | I |
| S/W | 0.5082 | ambiguous | 0.4795 | ambiguous | -1.066 | Destabilizing | 0.935 | D | 0.56 | neutral | None | None | None | None | I |
| S/Y | 0.2768 | likely_benign | 0.2447 | benign | -0.791 | Destabilizing | 0.555 | D | 0.488 | 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.