Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21548 | 64867;64868;64869 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| N2AB | 19907 | 59944;59945;59946 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| N2A | 18980 | 57163;57164;57165 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| N2B | 12483 | 37672;37673;37674 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| Novex-1 | 12608 | 38047;38048;38049 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| Novex-2 | 12675 | 38248;38249;38250 | chr2:178585102;178585101;178585100 | chr2:179449829;179449828;179449827 |
| 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/E | None | None | 0.425 | N | 0.335 | 0.069 | 0.343560092441 | gnomAD-4.0.0 | 1.60851E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77747E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs749070255  |
-0.305 | 0.975 | N | 0.589 | 0.414 | 0.686361129187 | gnomAD-2.1.1 | 7.26E-06 | None | None | None | None | N | None | 4.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.9E-06 | 0 |
| D/Y | rs749070255 |
-0.305 | 0.975 | N | 0.589 | 0.414 | 0.686361129187 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/Y | rs749070255 |
-0.305 | 0.975 | N | 0.589 | 0.414 | 0.686361129187 | gnomAD-4.0.0 | 1.43147E-05 | None | None | None | None | N | None | 1.3434E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.87006E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1007 | likely_benign | 0.0784 | benign | -0.455 | Destabilizing | 0.002 | N | 0.245 | neutral | N | 0.444995055 | None | None | N |
| D/C | 0.4874 | ambiguous | 0.4305 | ambiguous | 0.067 | Stabilizing | 0.944 | D | 0.548 | neutral | None | None | None | None | N |
| D/E | 0.1731 | likely_benign | 0.1381 | benign | -0.653 | Destabilizing | 0.425 | N | 0.335 | neutral | N | 0.496578669 | None | None | N |
| D/F | 0.5437 | ambiguous | 0.4814 | ambiguous | -0.537 | Destabilizing | 0.944 | D | 0.602 | neutral | None | None | None | None | N |
| D/G | 0.217 | likely_benign | 0.2002 | benign | -0.693 | Destabilizing | 0.27 | N | 0.445 | neutral | N | 0.495051307 | None | None | N |
| D/H | 0.3144 | likely_benign | 0.2702 | benign | -0.71 | Destabilizing | 0.975 | D | 0.465 | neutral | N | 0.501634672 | None | None | N |
| D/I | 0.2754 | likely_benign | 0.1942 | benign | 0.135 | Stabilizing | 0.031 | N | 0.357 | neutral | None | None | None | None | N |
| D/K | 0.4196 | ambiguous | 0.3255 | benign | 0.094 | Stabilizing | 0.704 | D | 0.439 | neutral | None | None | None | None | N |
| D/L | 0.349 | ambiguous | 0.2612 | benign | 0.135 | Stabilizing | 0.329 | N | 0.5 | neutral | None | None | None | None | N |
| D/M | 0.4854 | ambiguous | 0.3871 | ambiguous | 0.517 | Stabilizing | 0.944 | D | 0.569 | neutral | None | None | None | None | N |
| D/N | 0.1177 | likely_benign | 0.0927 | benign | -0.173 | Destabilizing | 0.642 | D | 0.41 | neutral | N | 0.519706245 | None | None | N |
| D/P | 0.9651 | likely_pathogenic | 0.9689 | pathogenic | -0.038 | Destabilizing | 0.828 | D | 0.517 | neutral | None | None | None | None | N |
| D/Q | 0.3367 | likely_benign | 0.2772 | benign | -0.159 | Destabilizing | 0.944 | D | 0.428 | neutral | None | None | None | None | N |
| D/R | 0.4595 | ambiguous | 0.3801 | ambiguous | 0.131 | Stabilizing | 0.944 | D | 0.581 | neutral | None | None | None | None | N |
| D/S | 0.1021 | likely_benign | 0.085 | benign | -0.314 | Destabilizing | 0.329 | N | 0.311 | neutral | None | None | None | None | N |
| D/T | 0.1632 | likely_benign | 0.1227 | benign | -0.132 | Destabilizing | 0.013 | N | 0.133 | neutral | None | None | None | None | N |
| D/V | 0.16 | likely_benign | 0.1154 | benign | -0.038 | Destabilizing | 0.01 | N | 0.285 | neutral | N | 0.454769332 | None | None | N |
| D/W | 0.9215 | likely_pathogenic | 0.9087 | pathogenic | -0.435 | Destabilizing | 0.995 | D | 0.595 | neutral | None | None | None | None | N |
| D/Y | 0.2923 | likely_benign | 0.2335 | benign | -0.302 | Destabilizing | 0.975 | D | 0.589 | neutral | N | 0.513244467 | 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.