Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19733 | 59422;59423;59424 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| N2AB | 18092 | 54499;54500;54501 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| N2A | 17165 | 51718;51719;51720 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| N2B | 10668 | 32227;32228;32229 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| Novex-1 | 10793 | 32602;32603;32604 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| Novex-2 | 10860 | 32803;32804;32805 | chr2:178592922;178592921;178592920 | chr2:179457649;179457648;179457647 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs749461231  |
0.008 | 0.982 | N | 0.456 | 0.346 | 0.36076525451 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs749461231 |
0.008 | 0.982 | N | 0.456 | 0.346 | 0.36076525451 | gnomAD-4.0.0 | 1.59166E-06 | None | None | None | None | N | None | 5.65931E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs749461231 |
-0.697 | 0.885 | N | 0.45 | 0.114 | 0.130388298395 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs749461231 |
-0.697 | 0.885 | N | 0.45 | 0.114 | 0.130388298395 | gnomAD-4.0.0 | 1.59166E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43283E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1183 | likely_benign | 0.1177 | benign | -0.582 | Destabilizing | 0.046 | N | 0.285 | neutral | N | 0.503357421 | None | None | N |
| T/C | 0.438 | ambiguous | 0.4882 | ambiguous | -0.273 | Destabilizing | 0.999 | D | 0.493 | neutral | None | None | None | None | N |
| T/D | 0.3296 | likely_benign | 0.2923 | benign | -0.039 | Destabilizing | 0.973 | D | 0.39 | neutral | None | None | None | None | N |
| T/E | 0.3244 | likely_benign | 0.2998 | benign | -0.097 | Destabilizing | 0.986 | D | 0.387 | neutral | None | None | None | None | N |
| T/F | 0.2768 | likely_benign | 0.296 | benign | -0.929 | Destabilizing | 0.998 | D | 0.602 | neutral | None | None | None | None | N |
| T/G | 0.2441 | likely_benign | 0.2465 | benign | -0.76 | Destabilizing | 0.91 | D | 0.473 | neutral | None | None | None | None | N |
| T/H | 0.2516 | likely_benign | 0.2491 | benign | -1.056 | Destabilizing | 0.998 | D | 0.595 | neutral | None | None | None | None | N |
| T/I | 0.2359 | likely_benign | 0.2493 | benign | -0.224 | Destabilizing | 0.982 | D | 0.456 | neutral | N | 0.517404153 | None | None | N |
| T/K | 0.2119 | likely_benign | 0.2021 | benign | -0.542 | Destabilizing | 0.986 | D | 0.388 | neutral | None | None | None | None | N |
| T/L | 0.1097 | likely_benign | 0.1184 | benign | -0.224 | Destabilizing | 0.953 | D | 0.407 | neutral | None | None | None | None | N |
| T/M | 0.1226 | likely_benign | 0.1272 | benign | 0.129 | Stabilizing | 0.999 | D | 0.475 | neutral | None | None | None | None | N |
| T/N | 0.1216 | likely_benign | 0.1168 | benign | -0.333 | Destabilizing | 0.322 | N | 0.237 | neutral | N | 0.485195734 | None | None | N |
| T/P | 0.4507 | ambiguous | 0.3404 | ambiguous | -0.313 | Destabilizing | 0.991 | D | 0.452 | neutral | N | 0.4641594 | None | None | N |
| T/Q | 0.2475 | likely_benign | 0.2431 | benign | -0.588 | Destabilizing | 0.993 | D | 0.459 | neutral | None | None | None | None | N |
| T/R | 0.2235 | likely_benign | 0.2137 | benign | -0.216 | Destabilizing | 0.993 | D | 0.453 | neutral | None | None | None | None | N |
| T/S | 0.0998 | likely_benign | 0.1004 | benign | -0.579 | Destabilizing | 0.885 | D | 0.45 | neutral | N | 0.48026713 | None | None | N |
| T/V | 0.1932 | likely_benign | 0.2124 | benign | -0.313 | Destabilizing | 0.91 | D | 0.386 | neutral | None | None | None | None | N |
| T/W | 0.6706 | likely_pathogenic | 0.677 | pathogenic | -0.878 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | N |
| T/Y | 0.3212 | likely_benign | 0.3358 | benign | -0.635 | Destabilizing | 0.998 | D | 0.604 | 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.