Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14452 | 43579;43580;43581 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| N2AB | 12811 | 38656;38657;38658 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| N2A | 11884 | 35875;35876;35877 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| N2B | 5387 | 16384;16385;16386 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| Novex-1 | 5512 | 16759;16760;16761 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| Novex-2 | 5579 | 16960;16961;16962 | chr2:178632652;178632651;178632650 | chr2:179497379;179497378;179497377 |
| 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/G | rs367791276  |
-1.537 | 0.024 | D | 0.255 | 0.51 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs367791276 |
-1.537 | 0.024 | D | 0.255 | 0.51 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/G | rs367791276 |
-1.537 | 0.024 | D | 0.255 | 0.51 | None | gnomAD-4.0.0 | 6.57514E-06 | None | None | None | None | N | None | 2.41301E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs528741819 |
-0.188 | 0.171 | D | 0.471 | 0.451 | 0.356690202451 | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 2.41E-05 | 4.59016E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/I | rs528741819 |
-0.188 | 0.171 | D | 0.471 | 0.451 | 0.356690202451 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/I | rs528741819 |
-0.188 | 0.171 | D | 0.471 | 0.451 | 0.356690202451 | gnomAD-4.0.0 | 8.67692E-06 | None | None | None | None | N | None | 1.33308E-05 | 1.83388E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20195E-05 |
| R/K | None | None | None | N | 0.066 | 0.255 | 0.128392430309 | gnomAD-4.0.0 | 6.84321E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99612E-07 | 0 | 0 |
| R/S | rs374231453 |
-1.176 | 0.012 | D | 0.283 | 0.248 | 0.290962096972 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| R/S | rs374231453 |
-1.176 | 0.012 | D | 0.283 | 0.248 | 0.290962096972 | gnomAD-4.0.0 | 6.84312E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99603E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2863 | likely_benign | 0.2935 | benign | -1.004 | Destabilizing | 0.007 | N | 0.269 | neutral | None | None | None | None | N |
| R/C | 0.2357 | likely_benign | 0.245 | benign | -0.896 | Destabilizing | 0.864 | D | 0.378 | neutral | None | None | None | None | N |
| R/D | 0.4752 | ambiguous | 0.4681 | ambiguous | 0.056 | Stabilizing | 0.072 | N | 0.315 | neutral | None | None | None | None | N |
| R/E | 0.2773 | likely_benign | 0.2688 | benign | 0.198 | Stabilizing | 0.016 | N | 0.213 | neutral | None | None | None | None | N |
| R/F | 0.5263 | ambiguous | 0.5343 | ambiguous | -0.833 | Destabilizing | 0.628 | D | 0.409 | neutral | None | None | None | None | N |
| R/G | 0.1635 | likely_benign | 0.1681 | benign | -1.317 | Destabilizing | 0.024 | N | 0.255 | neutral | D | 0.543660559 | None | None | N |
| R/H | 0.1219 | likely_benign | 0.1167 | benign | -1.621 | Destabilizing | 0.356 | N | 0.303 | neutral | None | None | None | None | N |
| R/I | 0.1906 | likely_benign | 0.22 | benign | -0.155 | Destabilizing | 0.171 | N | 0.471 | neutral | D | 0.596703934 | None | None | N |
| R/K | 0.0665 | likely_benign | 0.0654 | benign | -0.73 | Destabilizing | None | N | 0.066 | neutral | N | 0.394621891 | None | None | N |
| R/L | 0.2197 | likely_benign | 0.2279 | benign | -0.155 | Destabilizing | 0.031 | N | 0.255 | neutral | None | None | None | None | N |
| R/M | 0.1965 | likely_benign | 0.2058 | benign | -0.499 | Destabilizing | 0.628 | D | 0.342 | neutral | None | None | None | None | N |
| R/N | 0.3475 | ambiguous | 0.3474 | ambiguous | -0.315 | Destabilizing | 0.072 | N | 0.198 | neutral | None | None | None | None | N |
| R/P | 0.6383 | likely_pathogenic | 0.6041 | pathogenic | -0.418 | Destabilizing | 0.136 | N | 0.422 | neutral | None | None | None | None | N |
| R/Q | 0.1103 | likely_benign | 0.1056 | benign | -0.445 | Destabilizing | 0.038 | N | 0.227 | neutral | None | None | None | None | N |
| R/S | 0.3011 | likely_benign | 0.3104 | benign | -1.181 | Destabilizing | 0.012 | N | 0.283 | neutral | D | 0.522617724 | None | None | N |
| R/T | 0.1493 | likely_benign | 0.1556 | benign | -0.84 | Destabilizing | None | N | 0.151 | neutral | D | 0.525043835 | None | None | N |
| R/V | 0.2835 | likely_benign | 0.302 | benign | -0.418 | Destabilizing | 0.072 | N | 0.346 | neutral | None | None | None | None | N |
| R/W | 0.2347 | likely_benign | 0.222 | benign | -0.474 | Destabilizing | 0.864 | D | 0.393 | neutral | None | None | None | None | N |
| R/Y | 0.405 | ambiguous | 0.3989 | ambiguous | -0.197 | Destabilizing | 0.356 | N | 0.373 | 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.