Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20499 | 61720;61721;61722 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| N2AB | 18858 | 56797;56798;56799 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| N2A | 17931 | 54016;54017;54018 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| N2B | 11434 | 34525;34526;34527 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| Novex-1 | 11559 | 34900;34901;34902 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| Novex-2 | 11626 | 35101;35102;35103 | chr2:178590230;178590229;178590228 | chr2:179454957;179454956;179454955 |
| 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/Q | rs201286988  |
-0.212 | 0.844 | N | 0.536 | 0.22 | None | gnomAD-2.1.1 | 3.03E-05 | None | None | None | None | N | None | 6.57E-05 | 3.11E-05 | None | 0 | 5.69E-05 | None | 0 | None | 0 | 3.77E-05 | 0 |
| R/Q | rs201286988 |
-0.212 | 0.844 | N | 0.536 | 0.22 | None | gnomAD-4.0.0 | 3.11903E-05 | None | None | None | None | N | None | 0 | 2.33318E-05 | None | 0 | 0 | None | 1.90078E-05 | 0 | 3.80906E-05 | 0 | 1.68011E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5839 | likely_pathogenic | 0.6038 | pathogenic | 0.07 | Stabilizing | 0.345 | N | 0.533 | neutral | None | None | None | None | N |
| R/C | 0.322 | likely_benign | 0.3098 | benign | -0.038 | Destabilizing | 0.991 | D | 0.575 | neutral | None | None | None | None | N |
| R/D | 0.8504 | likely_pathogenic | 0.8519 | pathogenic | -0.018 | Destabilizing | 0.818 | D | 0.596 | neutral | None | None | None | None | N |
| R/E | 0.6293 | likely_pathogenic | 0.6212 | pathogenic | 0.092 | Stabilizing | 0.39 | N | 0.518 | neutral | None | None | None | None | N |
| R/F | 0.6626 | likely_pathogenic | 0.6834 | pathogenic | 0.095 | Stabilizing | 0.39 | N | 0.59 | neutral | None | None | None | None | N |
| R/G | 0.5187 | ambiguous | 0.5343 | ambiguous | -0.195 | Destabilizing | 0.71 | D | 0.573 | neutral | N | 0.484504695 | None | None | N |
| R/H | 0.169 | likely_benign | 0.1574 | benign | -0.783 | Destabilizing | 0.818 | D | 0.589 | neutral | None | None | None | None | N |
| R/I | 0.4051 | ambiguous | 0.4251 | ambiguous | 0.754 | Stabilizing | 0.39 | N | 0.597 | neutral | None | None | None | None | N |
| R/K | 0.159 | likely_benign | 0.1505 | benign | 0.009 | Stabilizing | 0.002 | N | 0.147 | neutral | None | None | None | None | N |
| R/L | 0.385 | ambiguous | 0.4065 | ambiguous | 0.754 | Stabilizing | 0.003 | N | 0.294 | neutral | N | 0.501197842 | None | None | N |
| R/M | 0.4478 | ambiguous | 0.4457 | ambiguous | 0.134 | Stabilizing | 0.818 | D | 0.621 | neutral | None | None | None | None | N |
| R/N | 0.7093 | likely_pathogenic | 0.7247 | pathogenic | 0.221 | Stabilizing | 0.561 | D | 0.548 | neutral | None | None | None | None | N |
| R/P | 0.9314 | likely_pathogenic | 0.943 | pathogenic | 0.549 | Stabilizing | 0.946 | D | 0.599 | neutral | N | 0.449750301 | None | None | N |
| R/Q | 0.1998 | likely_benign | 0.1901 | benign | 0.202 | Stabilizing | 0.844 | D | 0.536 | neutral | N | 0.490575416 | None | None | N |
| R/S | 0.6584 | likely_pathogenic | 0.6723 | pathogenic | -0.121 | Destabilizing | 0.561 | D | 0.567 | neutral | None | None | None | None | N |
| R/T | 0.3854 | ambiguous | 0.3868 | ambiguous | 0.151 | Stabilizing | 0.561 | D | 0.565 | neutral | None | None | None | None | N |
| R/V | 0.4444 | ambiguous | 0.4675 | ambiguous | 0.549 | Stabilizing | 0.39 | N | 0.573 | neutral | None | None | None | None | N |
| R/W | 0.2886 | likely_benign | 0.2725 | benign | 0.106 | Stabilizing | 0.972 | D | 0.576 | neutral | None | None | None | None | N |
| R/Y | 0.5368 | ambiguous | 0.5298 | ambiguous | 0.489 | Stabilizing | 0.007 | N | 0.291 | 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.