Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30045 | 90358;90359;90360 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| N2AB | 28404 | 85435;85436;85437 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| N2A | 27477 | 82654;82655;82656 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| N2B | 20980 | 63163;63164;63165 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| Novex-1 | 21105 | 63538;63539;63540 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| Novex-2 | 21172 | 63739;63740;63741 | chr2:178552767;178552766;178552765 | chr2:179417494;179417493;179417492 |
| 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/A | None | None | 0.454 | N | 0.402 | 0.169 | 0.170165803431 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/I | rs763963229  |
-0.356 | 0.966 | N | 0.439 | 0.215 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 3.59712E-04 | 7.8E-06 | 0 |
| T/I | rs763963229 |
-0.356 | 0.966 | N | 0.439 | 0.215 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.8843E-04 | 0 | 0 | 0 | 0 |
| T/I | rs763963229 |
-0.356 | 0.966 | N | 0.439 | 0.215 | None | gnomAD-4.0.0 | 1.3632E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 2.49961E-04 | 0 | 5.08538E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1067 | likely_benign | 0.1021 | benign | -0.917 | Destabilizing | 0.454 | N | 0.402 | neutral | N | 0.51005968 | None | None | N |
| T/C | 0.5094 | ambiguous | 0.4951 | ambiguous | -0.626 | Destabilizing | 0.998 | D | 0.453 | neutral | None | None | None | None | N |
| T/D | 0.3047 | likely_benign | 0.2754 | benign | -0.35 | Destabilizing | 0.728 | D | 0.43 | neutral | None | None | None | None | N |
| T/E | 0.3305 | likely_benign | 0.293 | benign | -0.379 | Destabilizing | 0.842 | D | 0.435 | neutral | None | None | None | None | N |
| T/F | 0.3013 | likely_benign | 0.2753 | benign | -1.253 | Destabilizing | 0.991 | D | 0.496 | neutral | None | None | None | None | N |
| T/G | 0.2323 | likely_benign | 0.2265 | benign | -1.109 | Destabilizing | 0.016 | N | 0.283 | neutral | None | None | None | None | N |
| T/H | 0.2499 | likely_benign | 0.2364 | benign | -1.461 | Destabilizing | 0.993 | D | 0.49 | neutral | None | None | None | None | N |
| T/I | 0.3669 | ambiguous | 0.333 | benign | -0.506 | Destabilizing | 0.966 | D | 0.439 | neutral | N | 0.47553043 | None | None | N |
| T/K | 0.2554 | likely_benign | 0.2303 | benign | -0.638 | Destabilizing | 0.801 | D | 0.433 | neutral | N | 0.460246936 | None | None | N |
| T/L | 0.1548 | likely_benign | 0.1457 | benign | -0.506 | Destabilizing | 0.842 | D | 0.436 | neutral | None | None | None | None | N |
| T/M | 0.1084 | likely_benign | 0.1037 | benign | -0.056 | Destabilizing | 0.998 | D | 0.442 | neutral | None | None | None | None | N |
| T/N | 0.0857 | likely_benign | 0.0856 | benign | -0.557 | Destabilizing | 0.067 | N | 0.24 | neutral | None | None | None | None | N |
| T/P | 0.6058 | likely_pathogenic | 0.4795 | ambiguous | -0.614 | Destabilizing | 0.966 | D | 0.441 | neutral | N | 0.494141664 | None | None | N |
| T/Q | 0.2479 | likely_benign | 0.2258 | benign | -0.862 | Destabilizing | 0.974 | D | 0.438 | neutral | None | None | None | None | N |
| T/R | 0.2432 | likely_benign | 0.2077 | benign | -0.347 | Destabilizing | 0.934 | D | 0.442 | neutral | N | 0.406471166 | None | None | N |
| T/S | 0.0889 | likely_benign | 0.0899 | benign | -0.847 | Destabilizing | 0.022 | N | 0.105 | neutral | N | 0.429806598 | None | None | N |
| T/V | 0.2789 | likely_benign | 0.2682 | benign | -0.614 | Destabilizing | 0.842 | D | 0.445 | neutral | None | None | None | None | N |
| T/W | 0.6716 | likely_pathogenic | 0.6223 | pathogenic | -1.132 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | N |
| T/Y | 0.2659 | likely_benign | 0.2485 | benign | -0.884 | Destabilizing | 0.991 | D | 0.498 | 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.