Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21701 | 65326;65327;65328 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| N2AB | 20060 | 60403;60404;60405 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| N2A | 19133 | 57622;57623;57624 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| N2B | 12636 | 38131;38132;38133 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| Novex-1 | 12761 | 38506;38507;38508 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| Novex-2 | 12828 | 38707;38708;38709 | chr2:178584450;178584449;178584448 | chr2:179449177;179449176;179449175 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | rs756852802  |
0.327 | 1.0 | N | 0.707 | 0.384 | 0.594763190098 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| R/I | rs756852802 |
0.327 | 1.0 | N | 0.707 | 0.384 | 0.594763190098 | gnomAD-4.0.0 | 6.84401E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52678E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs756852802 |
-0.311 | 1.0 | N | 0.641 | 0.385 | 0.516715673709 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| R/T | rs756852802 |
-0.311 | 1.0 | N | 0.641 | 0.385 | 0.516715673709 | gnomAD-4.0.0 | 1.3688E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7993E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8272 | likely_pathogenic | 0.7609 | pathogenic | -0.408 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| R/C | 0.5269 | ambiguous | 0.386 | ambiguous | -0.414 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/D | 0.9743 | likely_pathogenic | 0.9538 | pathogenic | -0.004 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/E | 0.8291 | likely_pathogenic | 0.744 | pathogenic | 0.111 | Stabilizing | 0.999 | D | 0.674 | neutral | None | None | None | None | N |
| R/F | 0.9365 | likely_pathogenic | 0.8836 | pathogenic | -0.358 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/G | 0.7474 | likely_pathogenic | 0.6515 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.481808713 | None | None | N |
| R/H | 0.3534 | ambiguous | 0.2557 | benign | -1.183 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/I | 0.7173 | likely_pathogenic | 0.6248 | pathogenic | 0.326 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | N | 0.488734685 | None | None | N |
| R/K | 0.133 | likely_benign | 0.1316 | benign | -0.397 | Destabilizing | 0.997 | D | 0.523 | neutral | N | 0.406193446 | None | None | N |
| R/L | 0.6641 | likely_pathogenic | 0.5314 | ambiguous | 0.326 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | N |
| R/M | 0.6843 | likely_pathogenic | 0.589 | pathogenic | -0.127 | Destabilizing | 1.0 | D | 0.657 | neutral | None | None | None | None | N |
| R/N | 0.9321 | likely_pathogenic | 0.8886 | pathogenic | -0.046 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/P | 0.9221 | likely_pathogenic | 0.8966 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/Q | 0.2435 | likely_benign | 0.1859 | benign | -0.14 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/S | 0.9283 | likely_pathogenic | 0.8837 | pathogenic | -0.618 | Destabilizing | 1.0 | D | 0.642 | neutral | N | 0.467665979 | None | None | N |
| R/T | 0.8148 | likely_pathogenic | 0.7413 | pathogenic | -0.328 | Destabilizing | 1.0 | D | 0.641 | neutral | N | 0.474591952 | None | None | N |
| R/V | 0.8018 | likely_pathogenic | 0.7199 | pathogenic | 0.103 | Stabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| R/W | 0.5817 | likely_pathogenic | 0.4415 | ambiguous | -0.196 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8486 | likely_pathogenic | 0.7399 | pathogenic | 0.144 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | 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.