Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22088 | 66487;66488;66489 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| N2AB | 20447 | 61564;61565;61566 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| N2A | 19520 | 58783;58784;58785 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| N2B | 13023 | 39292;39293;39294 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| Novex-1 | 13148 | 39667;39668;39669 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| Novex-2 | 13215 | 39868;39869;39870 | chr2:178582107;178582106;178582105 | chr2:179446834;179446833;179446832 |
| 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/A | rs1559509011  |
None | 0.954 | N | 0.487 | 0.28 | 0.336155897331 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| T/A | rs1559509011 |
None | 0.954 | N | 0.487 | 0.28 | 0.336155897331 | gnomAD-4.0.0 | 1.59308E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77562E-05 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs886044538 |
None | 0.998 | N | 0.533 | 0.364 | 0.417334834585 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | rs886044538 |
None | 0.998 | N | 0.533 | 0.364 | 0.417334834585 | gnomAD-4.0.0 | 1.97314E-05 | None | None | None | None | I | None | 7.24218E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | rs1559509011 |
None | 0.998 | D | 0.665 | 0.473 | 0.488827753106 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 0 | 0 | 4.78927E-04 |
| T/P | rs1559509011 |
None | 0.998 | D | 0.665 | 0.473 | 0.488827753106 | gnomAD-4.0.0 | 1.31427E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.40136E-03 | 0 | 0 | 4.73934E-04 |
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 | 0.1341 | likely_benign | 0.1112 | benign | -0.786 | Destabilizing | 0.954 | D | 0.487 | neutral | N | 0.488324632 | None | None | I |
| T/C | 0.5534 | ambiguous | 0.4673 | ambiguous | -0.44 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| T/D | 0.6049 | likely_pathogenic | 0.5041 | ambiguous | 0.259 | Stabilizing | 0.999 | D | 0.645 | neutral | None | None | None | None | I |
| T/E | 0.4525 | ambiguous | 0.3523 | ambiguous | 0.273 | Stabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| T/F | 0.3931 | ambiguous | 0.3131 | benign | -0.827 | Destabilizing | 0.991 | D | 0.729 | prob.delet. | None | None | None | None | I |
| T/G | 0.4095 | ambiguous | 0.3214 | benign | -1.048 | Destabilizing | 0.999 | D | 0.599 | neutral | None | None | None | None | I |
| T/H | 0.4349 | ambiguous | 0.3396 | benign | -1.237 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| T/I | 0.1867 | likely_benign | 0.1562 | benign | -0.178 | Destabilizing | 0.925 | D | 0.515 | neutral | N | 0.510787612 | None | None | I |
| T/K | 0.4221 | ambiguous | 0.3171 | benign | -0.487 | Destabilizing | 0.999 | D | 0.58 | neutral | None | None | None | None | I |
| T/L | 0.0988 | likely_benign | 0.0841 | benign | -0.178 | Destabilizing | 0.041 | N | 0.253 | neutral | None | None | None | None | I |
| T/M | 0.1032 | likely_benign | 0.093 | benign | -0.008 | Destabilizing | 0.991 | D | 0.675 | prob.neutral | None | None | None | None | I |
| T/N | 0.195 | likely_benign | 0.1647 | benign | -0.459 | Destabilizing | 0.998 | D | 0.533 | neutral | N | 0.478298226 | None | None | I |
| T/P | 0.6643 | likely_pathogenic | 0.6048 | pathogenic | -0.348 | Destabilizing | 0.998 | D | 0.665 | neutral | D | 0.526142984 | None | None | I |
| T/Q | 0.3444 | ambiguous | 0.2667 | benign | -0.568 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| T/R | 0.4156 | ambiguous | 0.2906 | benign | -0.327 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | I |
| T/S | 0.1485 | likely_benign | 0.1224 | benign | -0.817 | Destabilizing | 0.993 | D | 0.475 | neutral | N | 0.462879022 | None | None | I |
| T/V | 0.1665 | likely_benign | 0.1459 | benign | -0.348 | Destabilizing | 0.871 | D | 0.507 | neutral | None | None | None | None | I |
| T/W | 0.7681 | likely_pathogenic | 0.6916 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | I |
| T/Y | 0.4724 | ambiguous | 0.3805 | ambiguous | -0.505 | Destabilizing | 0.999 | D | 0.733 | prob.delet. | 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.