Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30043 | 90352;90353;90354 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| N2AB | 28402 | 85429;85430;85431 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| N2A | 27475 | 82648;82649;82650 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| N2B | 20978 | 63157;63158;63159 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| Novex-1 | 21103 | 63532;63533;63534 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| Novex-2 | 21170 | 63733;63734;63735 | chr2:178552773;178552772;178552771 | chr2:179417500;179417499;179417498 |
| 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 | rs757241713  |
-1.092 | 0.489 | N | 0.449 | 0.172 | 0.166414681773 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs757241713 |
-1.092 | 0.489 | N | 0.449 | 0.172 | 0.166414681773 | gnomAD-4.0.0 | 1.36834E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52003E-05 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| T/I | None | None | 0.971 | D | 0.68 | 0.448 | 0.637981554935 | 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/S | None | None | 0.058 | N | 0.23 | 0.044 | 0.128392430309 | gnomAD-4.0.0 | 2.05251E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69829E-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 | 0.1675 | likely_benign | 0.1576 | benign | -0.678 | Destabilizing | 0.489 | N | 0.449 | neutral | N | 0.483515693 | None | None | N |
| T/C | 0.5866 | likely_pathogenic | 0.5762 | pathogenic | -0.471 | Destabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | N |
| T/D | 0.4519 | ambiguous | 0.4466 | ambiguous | -0.789 | Destabilizing | 0.956 | D | 0.629 | neutral | None | None | None | None | N |
| T/E | 0.5713 | likely_pathogenic | 0.5468 | ambiguous | -0.805 | Destabilizing | 0.956 | D | 0.632 | neutral | None | None | None | None | N |
| T/F | 0.6743 | likely_pathogenic | 0.6531 | pathogenic | -0.961 | Destabilizing | 0.978 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/G | 0.192 | likely_benign | 0.1925 | benign | -0.902 | Destabilizing | 0.754 | D | 0.549 | neutral | None | None | None | None | N |
| T/H | 0.4494 | ambiguous | 0.4399 | ambiguous | -1.299 | Destabilizing | 0.994 | D | 0.67 | neutral | None | None | None | None | N |
| T/I | 0.7503 | likely_pathogenic | 0.7214 | pathogenic | -0.178 | Destabilizing | 0.971 | D | 0.68 | prob.neutral | D | 0.533335461 | None | None | N |
| T/K | 0.3584 | ambiguous | 0.3339 | benign | -0.661 | Destabilizing | 0.89 | D | 0.635 | neutral | N | 0.485072629 | None | None | N |
| T/L | 0.3046 | likely_benign | 0.2763 | benign | -0.178 | Destabilizing | 0.86 | D | 0.575 | neutral | None | None | None | None | N |
| T/M | 0.2498 | likely_benign | 0.2305 | benign | 0.299 | Stabilizing | 0.998 | D | 0.639 | neutral | None | None | None | None | N |
| T/N | 0.1688 | likely_benign | 0.1636 | benign | -0.679 | Destabilizing | 0.915 | D | 0.618 | neutral | None | None | None | None | N |
| T/P | 0.7059 | likely_pathogenic | 0.6838 | pathogenic | -0.314 | Destabilizing | 0.971 | D | 0.68 | prob.neutral | N | 0.515231206 | None | None | N |
| T/Q | 0.3591 | ambiguous | 0.3369 | benign | -0.97 | Destabilizing | 0.956 | D | 0.673 | neutral | None | None | None | None | N |
| T/R | 0.3101 | likely_benign | 0.2829 | benign | -0.354 | Destabilizing | 0.942 | D | 0.683 | prob.neutral | N | 0.475348938 | None | None | N |
| T/S | 0.0841 | likely_benign | 0.0878 | benign | -0.857 | Destabilizing | 0.058 | N | 0.23 | neutral | N | 0.493969933 | None | None | N |
| T/V | 0.5305 | ambiguous | 0.4994 | ambiguous | -0.314 | Destabilizing | 0.86 | D | 0.539 | neutral | None | None | None | None | N |
| T/W | 0.8636 | likely_pathogenic | 0.8603 | pathogenic | -0.917 | Destabilizing | 0.998 | D | 0.654 | neutral | None | None | None | None | N |
| T/Y | 0.6258 | likely_pathogenic | 0.6119 | pathogenic | -0.634 | Destabilizing | 0.993 | D | 0.708 | prob.delet. | 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.