Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21399 | 64420;64421;64422 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| N2AB | 19758 | 59497;59498;59499 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| N2A | 18831 | 56716;56717;56718 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| N2B | 12334 | 37225;37226;37227 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| Novex-1 | 12459 | 37600;37601;37602 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| Novex-2 | 12526 | 37801;37802;37803 | chr2:178586706;178586705;178586704 | chr2:179451433;179451432;179451431 |
| 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 | rs749018114  |
0.076 | 0.581 | N | 0.163 | 0.207 | None | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 9.95E-05 | 0 | None | 3.27E-05 | None | 0 | 2.67E-05 | 0 |
| D/N | rs749018114 |
0.076 | 0.581 | N | 0.163 | 0.207 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| D/N | rs749018114 |
0.076 | 0.581 | N | 0.163 | 0.207 | None | gnomAD-4.0.0 | 2.66592E-05 | None | None | None | None | I | None | 2.67208E-05 | 0 | None | 6.76315E-05 | 0 | None | 0 | 0 | 3.05248E-05 | 2.19674E-05 | 1.60185E-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 | 0.3452 | ambiguous | 0.302 | benign | -0.498 | Destabilizing | 0.989 | D | 0.579 | neutral | N | 0.497818315 | None | None | I |
| D/C | 0.8172 | likely_pathogenic | 0.7757 | pathogenic | -0.145 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | None | I |
| D/E | 0.304 | likely_benign | 0.2487 | benign | -0.459 | Destabilizing | 0.948 | D | 0.461 | neutral | N | 0.470535713 | None | None | I |
| D/F | 0.7779 | likely_pathogenic | 0.7526 | pathogenic | -0.362 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | I |
| D/G | 0.4323 | ambiguous | 0.3762 | ambiguous | -0.747 | Destabilizing | 0.978 | D | 0.511 | neutral | N | 0.504957718 | None | None | I |
| D/H | 0.4943 | ambiguous | 0.4344 | ambiguous | -0.482 | Destabilizing | 0.999 | D | 0.653 | neutral | N | 0.512769125 | None | None | I |
| D/I | 0.5192 | ambiguous | 0.4657 | ambiguous | 0.126 | Stabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | I |
| D/K | 0.7524 | likely_pathogenic | 0.6592 | pathogenic | -0.148 | Destabilizing | 0.983 | D | 0.611 | neutral | None | None | None | None | I |
| D/L | 0.5535 | ambiguous | 0.5064 | ambiguous | 0.126 | Stabilizing | 0.998 | D | 0.748 | deleterious | None | None | None | None | I |
| D/M | 0.7584 | likely_pathogenic | 0.7208 | pathogenic | 0.407 | Stabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | I |
| D/N | 0.1396 | likely_benign | 0.1399 | benign | -0.408 | Destabilizing | 0.581 | D | 0.163 | neutral | N | 0.45146995 | None | None | I |
| D/P | 0.9618 | likely_pathogenic | 0.9485 | pathogenic | -0.059 | Destabilizing | 0.999 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/Q | 0.5976 | likely_pathogenic | 0.5243 | ambiguous | -0.355 | Destabilizing | 0.998 | D | 0.63 | neutral | None | None | None | None | I |
| D/R | 0.742 | likely_pathogenic | 0.6682 | pathogenic | 0.017 | Stabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/S | 0.1787 | likely_benign | 0.1635 | benign | -0.576 | Destabilizing | 0.983 | D | 0.477 | neutral | None | None | None | None | I |
| D/T | 0.2543 | likely_benign | 0.2253 | benign | -0.387 | Destabilizing | 0.983 | D | 0.617 | neutral | None | None | None | None | I |
| D/V | 0.3603 | ambiguous | 0.3122 | benign | -0.059 | Destabilizing | 0.999 | D | 0.76 | deleterious | N | 0.450968517 | None | None | I |
| D/W | 0.9497 | likely_pathogenic | 0.9402 | pathogenic | -0.215 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| D/Y | 0.4413 | ambiguous | 0.379 | ambiguous | -0.146 | Destabilizing | 1.0 | D | 0.745 | deleterious | D | 0.523543479 | 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.