Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14807 | 44644;44645;44646 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| N2AB | 13166 | 39721;39722;39723 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| N2A | 12239 | 36940;36941;36942 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| N2B | 5742 | 17449;17450;17451 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| Novex-1 | 5867 | 17824;17825;17826 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| Novex-2 | 5934 | 18025;18026;18027 | chr2:178629306;178629305;178629304 | chr2:179494033;179494032;179494031 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs753053245  |
0.337 | 0.965 | N | 0.599 | 0.285 | 0.194818534648 | gnomAD-2.1.1 | 1.08E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 7.84E-06 | 0 |
| D/N | rs753053245 |
0.337 | 0.965 | N | 0.599 | 0.285 | 0.194818534648 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs753053245 |
0.337 | 0.965 | N | 0.599 | 0.285 | 0.194818534648 | gnomAD-4.0.0 | 2.60515E-05 | None | None | None | None | N | None | 1.33622E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.96846E-05 | 5.49716E-05 | 1.60349E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1368 | likely_benign | 0.1642 | benign | 0.055 | Stabilizing | 0.709 | D | 0.509 | neutral | N | 0.438149757 | None | None | N |
| D/C | 0.5947 | likely_pathogenic | 0.6484 | pathogenic | -0.054 | Destabilizing | 0.993 | D | 0.71 | prob.delet. | None | None | None | None | N |
| D/E | 0.0978 | likely_benign | 0.1012 | benign | -0.254 | Destabilizing | 0.004 | N | 0.327 | neutral | N | 0.448207685 | None | None | N |
| D/F | 0.5421 | ambiguous | 0.6489 | pathogenic | 0.013 | Stabilizing | 0.993 | D | 0.675 | neutral | None | None | None | None | N |
| D/G | 0.127 | likely_benign | 0.1558 | benign | -0.07 | Destabilizing | 0.581 | D | 0.518 | neutral | N | 0.439865128 | None | None | N |
| D/H | 0.2425 | likely_benign | 0.3045 | benign | 0.536 | Stabilizing | 0.99 | D | 0.622 | neutral | D | 0.544401296 | None | None | N |
| D/I | 0.3217 | likely_benign | 0.3951 | ambiguous | 0.316 | Stabilizing | 0.929 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/K | 0.2161 | likely_benign | 0.2855 | benign | 0.536 | Stabilizing | 0.764 | D | 0.537 | neutral | None | None | None | None | N |
| D/L | 0.2901 | likely_benign | 0.3572 | ambiguous | 0.316 | Stabilizing | 0.866 | D | 0.659 | neutral | None | None | None | None | N |
| D/M | 0.524 | ambiguous | 0.5811 | pathogenic | 0.148 | Stabilizing | 0.993 | D | 0.699 | prob.neutral | None | None | None | None | N |
| D/N | 0.0932 | likely_benign | 0.1102 | benign | 0.218 | Stabilizing | 0.965 | D | 0.599 | neutral | N | 0.446066394 | None | None | N |
| D/P | 0.3556 | ambiguous | 0.4052 | ambiguous | 0.248 | Stabilizing | 0.929 | D | 0.573 | neutral | None | None | None | None | N |
| D/Q | 0.2194 | likely_benign | 0.2609 | benign | 0.24 | Stabilizing | 0.764 | D | 0.618 | neutral | None | None | None | None | N |
| D/R | 0.2834 | likely_benign | 0.3594 | ambiguous | 0.722 | Stabilizing | 0.764 | D | 0.606 | neutral | None | None | None | None | N |
| D/S | 0.1028 | likely_benign | 0.1194 | benign | 0.152 | Stabilizing | 0.48 | N | 0.527 | neutral | None | None | None | None | N |
| D/T | 0.2118 | likely_benign | 0.2485 | benign | 0.26 | Stabilizing | 0.866 | D | 0.563 | neutral | None | None | None | None | N |
| D/V | 0.191 | likely_benign | 0.2388 | benign | 0.248 | Stabilizing | 0.83 | D | 0.654 | neutral | D | 0.545471924 | None | None | N |
| D/W | 0.8144 | likely_pathogenic | 0.8603 | pathogenic | 0.062 | Stabilizing | 0.993 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2434 | likely_benign | 0.3137 | benign | 0.241 | Stabilizing | 0.997 | D | 0.674 | neutral | D | 0.607054222 | None | None | N |
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.