Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22628 | 68107;68108;68109 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| N2AB | 20987 | 63184;63185;63186 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| N2A | 20060 | 60403;60404;60405 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| N2B | 13563 | 40912;40913;40914 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| Novex-1 | 13688 | 41287;41288;41289 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| Novex-2 | 13755 | 41488;41489;41490 | chr2:178579148;178579147;178579146 | chr2:179443875;179443874;179443873 |
| 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/A | None | None | None | N | 0.124 | 0.099 | 0.385249989106 | gnomAD-4.0.0 | 4.10603E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.5984E-06 | 0 | 3.31411E-05 |
| V/I | rs775731759  |
0.031 | 0.042 | N | 0.322 | 0.106 | None | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/I | rs775731759 |
0.031 | 0.042 | N | 0.322 | 0.106 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 1.20662E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs775731759 |
0.031 | 0.042 | N | 0.322 | 0.106 | None | gnomAD-4.0.0 | 7.6901E-06 | None | None | None | None | I | None | 1.01537E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0783 | likely_benign | 0.0721 | benign | -0.355 | Destabilizing | None | N | 0.124 | neutral | N | 0.412941352 | None | None | I |
| V/C | 0.5404 | ambiguous | 0.5318 | ambiguous | -0.818 | Destabilizing | 0.667 | D | 0.315 | neutral | None | None | None | None | I |
| V/D | 0.1922 | likely_benign | 0.1706 | benign | -0.35 | Destabilizing | 0.175 | N | 0.327 | neutral | N | 0.440840029 | None | None | I |
| V/E | 0.1822 | likely_benign | 0.1805 | benign | -0.469 | Destabilizing | 0.22 | N | 0.365 | neutral | None | None | None | None | I |
| V/F | 0.1608 | likely_benign | 0.1478 | benign | -0.748 | Destabilizing | 0.602 | D | 0.3 | neutral | N | 0.479051701 | None | None | I |
| V/G | 0.1174 | likely_benign | 0.108 | benign | -0.408 | Destabilizing | 0.042 | N | 0.347 | neutral | N | 0.448382077 | None | None | I |
| V/H | 0.3593 | ambiguous | 0.3493 | ambiguous | -0.036 | Destabilizing | 0.859 | D | 0.313 | neutral | None | None | None | None | I |
| V/I | 0.0741 | likely_benign | 0.0725 | benign | -0.358 | Destabilizing | 0.042 | N | 0.322 | neutral | N | 0.451326382 | None | None | I |
| V/K | 0.2087 | likely_benign | 0.2218 | benign | -0.389 | Destabilizing | 0.22 | N | 0.356 | neutral | None | None | None | None | I |
| V/L | 0.1367 | likely_benign | 0.1367 | benign | -0.358 | Destabilizing | 0.042 | N | 0.338 | neutral | N | 0.453673254 | None | None | I |
| V/M | 0.1071 | likely_benign | 0.1076 | benign | -0.564 | Destabilizing | 0.667 | D | 0.299 | neutral | None | None | None | None | I |
| V/N | 0.1341 | likely_benign | 0.1258 | benign | -0.203 | Destabilizing | 0.22 | N | 0.333 | neutral | None | None | None | None | I |
| V/P | 0.2363 | likely_benign | 0.2151 | benign | -0.329 | Destabilizing | 0.001 | N | 0.225 | neutral | None | None | None | None | I |
| V/Q | 0.2043 | likely_benign | 0.2089 | benign | -0.416 | Destabilizing | 0.667 | D | 0.361 | neutral | None | None | None | None | I |
| V/R | 0.2011 | likely_benign | 0.2155 | benign | 0.056 | Stabilizing | 0.497 | N | 0.345 | neutral | None | None | None | None | I |
| V/S | 0.0943 | likely_benign | 0.0872 | benign | -0.509 | Destabilizing | 0.002 | N | 0.132 | neutral | None | None | None | None | I |
| V/T | 0.084 | likely_benign | 0.0842 | benign | -0.536 | Destabilizing | 0.001 | N | 0.165 | neutral | None | None | None | None | I |
| V/W | 0.7092 | likely_pathogenic | 0.6993 | pathogenic | -0.802 | Destabilizing | 0.958 | D | 0.339 | neutral | None | None | None | None | I |
| V/Y | 0.412 | ambiguous | 0.3993 | ambiguous | -0.53 | Destabilizing | 0.667 | D | 0.298 | neutral | None | None | None | None | I |
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.