Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25886 | 77881;77882;77883 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| N2AB | 24245 | 72958;72959;72960 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| N2A | 23318 | 70177;70178;70179 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| N2B | 16821 | 50686;50687;50688 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| Novex-1 | 16946 | 51061;51062;51063 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| Novex-2 | 17013 | 51262;51263;51264 | chr2:178568476;178568475;178568474 | chr2:179433203;179433202;179433201 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs747738228  |
0.106 | 0.001 | N | 0.202 | 0.05 | 0.303781844768 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| V/L | rs747738228 |
0.106 | 0.001 | N | 0.202 | 0.05 | 0.303781844768 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 2.23724E-05 | None | 0 | 0 | None | 0 | 0 | 8.99606E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2686 | likely_benign | 0.2987 | benign | -0.423 | Destabilizing | 0.005 | N | 0.209 | neutral | N | 0.456906655 | None | None | N |
| V/C | 0.6255 | likely_pathogenic | 0.6218 | pathogenic | -0.64 | Destabilizing | 0.628 | D | 0.348 | neutral | None | None | None | None | N |
| V/D | 0.5286 | ambiguous | 0.599 | pathogenic | 0.17 | Stabilizing | 0.072 | N | 0.389 | neutral | None | None | None | None | N |
| V/E | 0.4171 | ambiguous | 0.4526 | ambiguous | 0.068 | Stabilizing | 0.055 | N | 0.371 | neutral | N | 0.456146187 | None | None | N |
| V/F | 0.1424 | likely_benign | 0.1489 | benign | -0.631 | Destabilizing | 0.072 | N | 0.386 | neutral | None | None | None | None | N |
| V/G | 0.3725 | ambiguous | 0.4141 | ambiguous | -0.563 | Destabilizing | 0.055 | N | 0.359 | neutral | N | 0.457920613 | None | None | N |
| V/H | 0.4515 | ambiguous | 0.4757 | ambiguous | -0.182 | Destabilizing | 0.864 | D | 0.329 | neutral | None | None | None | None | N |
| V/I | 0.057 | likely_benign | 0.0572 | benign | -0.203 | Destabilizing | None | N | 0.148 | neutral | N | 0.370859003 | None | None | N |
| V/K | 0.3362 | likely_benign | 0.3537 | ambiguous | -0.18 | Destabilizing | 0.072 | N | 0.365 | neutral | None | None | None | None | N |
| V/L | 0.1286 | likely_benign | 0.1222 | benign | -0.203 | Destabilizing | 0.001 | N | 0.202 | neutral | N | 0.454706964 | None | None | N |
| V/M | 0.1188 | likely_benign | 0.1152 | benign | -0.25 | Destabilizing | 0.214 | N | 0.365 | neutral | None | None | None | None | N |
| V/N | 0.2482 | likely_benign | 0.2747 | benign | 0.043 | Stabilizing | 0.214 | N | 0.375 | neutral | None | None | None | None | N |
| V/P | 0.9112 | likely_pathogenic | 0.9377 | pathogenic | -0.241 | Destabilizing | 0.356 | N | 0.368 | neutral | None | None | None | None | N |
| V/Q | 0.3173 | likely_benign | 0.3259 | benign | -0.184 | Destabilizing | 0.356 | N | 0.353 | neutral | None | None | None | None | N |
| V/R | 0.2791 | likely_benign | 0.2955 | benign | 0.224 | Stabilizing | 0.214 | N | 0.367 | neutral | None | None | None | None | N |
| V/S | 0.2409 | likely_benign | 0.2774 | benign | -0.413 | Destabilizing | 0.038 | N | 0.357 | neutral | None | None | None | None | N |
| V/T | 0.1611 | likely_benign | 0.1894 | benign | -0.408 | Destabilizing | None | N | 0.133 | neutral | None | None | None | None | N |
| V/W | 0.7433 | likely_pathogenic | 0.7533 | pathogenic | -0.692 | Destabilizing | 0.864 | D | 0.351 | neutral | None | None | None | None | N |
| V/Y | 0.4287 | ambiguous | 0.4434 | ambiguous | -0.358 | Destabilizing | 0.356 | N | 0.389 | 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.