Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20366 | 61321;61322;61323 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| N2AB | 18725 | 56398;56399;56400 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| N2A | 17798 | 53617;53618;53619 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| N2B | 11301 | 34126;34127;34128 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| Novex-1 | 11426 | 34501;34502;34503 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| Novex-2 | 11493 | 34702;34703;34704 | chr2:178590629;178590628;178590627 | chr2:179455356;179455355;179455354 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/S | rs200101317  |
-0.555 | 0.01 | N | 0.142 | 0.148 | 0.369495900351 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 8.5E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 0 |
| C/S | rs200101317 |
-0.555 | 0.01 | N | 0.142 | 0.148 | 0.369495900351 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.36E-05 | 0 | 0 |
| C/S | rs200101317 |
-0.555 | 0.01 | N | 0.142 | 0.148 | 0.369495900351 | gnomAD-4.0.0 | 2.66591E-05 | None | None | None | None | N | None | 0 | 1.00097E-04 | None | 0 | 0 | None | 0 | 0 | 2.96764E-05 | 0 | 3.20297E-05 |
| C/Y | rs2050006408 |
None | 0.976 | N | 0.575 | 0.232 | 0.51230852224 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 6.33473E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2495 | likely_benign | 0.2731 | benign | -0.713 | Destabilizing | 0.338 | N | 0.291 | neutral | None | None | None | None | N |
| C/D | 0.5466 | ambiguous | 0.633 | pathogenic | 0.248 | Stabilizing | 0.712 | D | 0.562 | neutral | None | None | None | None | N |
| C/E | 0.5595 | ambiguous | 0.5928 | pathogenic | 0.221 | Stabilizing | 0.897 | D | 0.591 | neutral | None | None | None | None | N |
| C/F | 0.1422 | likely_benign | 0.164 | benign | -0.592 | Destabilizing | 0.93 | D | 0.599 | neutral | N | 0.45127987 | None | None | N |
| C/G | 0.1379 | likely_benign | 0.1639 | benign | -0.866 | Destabilizing | 0.483 | N | 0.505 | neutral | N | 0.454762892 | None | None | N |
| C/H | 0.3166 | likely_benign | 0.3625 | ambiguous | -0.806 | Destabilizing | 0.995 | D | 0.578 | neutral | None | None | None | None | N |
| C/I | 0.3357 | likely_benign | 0.3331 | benign | -0.389 | Destabilizing | 0.897 | D | 0.435 | neutral | None | None | None | None | N |
| C/K | 0.5032 | ambiguous | 0.5534 | ambiguous | -0.128 | Destabilizing | 0.712 | D | 0.561 | neutral | None | None | None | None | N |
| C/L | 0.2987 | likely_benign | 0.3089 | benign | -0.389 | Destabilizing | 0.553 | D | 0.386 | neutral | None | None | None | None | N |
| C/M | 0.4119 | ambiguous | 0.4009 | ambiguous | 0.086 | Stabilizing | 0.982 | D | 0.399 | neutral | None | None | None | None | N |
| C/N | 0.3177 | likely_benign | 0.345 | ambiguous | 0.233 | Stabilizing | 0.897 | D | 0.592 | neutral | None | None | None | None | N |
| C/P | 0.9116 | likely_pathogenic | 0.9577 | pathogenic | -0.473 | Destabilizing | 0.946 | D | 0.627 | neutral | None | None | None | None | N |
| C/Q | 0.342 | ambiguous | 0.3638 | ambiguous | 0.064 | Stabilizing | 0.946 | D | 0.66 | prob.neutral | None | None | None | None | N |
| C/R | 0.2469 | likely_benign | 0.2949 | benign | 0.24 | Stabilizing | 0.868 | D | 0.628 | neutral | N | 0.402467203 | None | None | N |
| C/S | 0.1578 | likely_benign | 0.1651 | benign | -0.234 | Destabilizing | 0.01 | N | 0.142 | neutral | N | 0.4628623 | None | None | N |
| C/T | 0.2542 | likely_benign | 0.2545 | benign | -0.141 | Destabilizing | 0.032 | N | 0.253 | neutral | None | None | None | None | N |
| C/V | 0.2728 | likely_benign | 0.2691 | benign | -0.473 | Destabilizing | 0.553 | D | 0.449 | neutral | None | None | None | None | N |
| C/W | 0.3798 | ambiguous | 0.4544 | ambiguous | -0.544 | Destabilizing | 0.993 | D | 0.618 | neutral | N | 0.460372468 | None | None | N |
| C/Y | 0.1949 | likely_benign | 0.241 | benign | -0.44 | Destabilizing | 0.976 | D | 0.575 | neutral | N | 0.502458052 | 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.