Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31565 | 94918;94919;94920 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| N2AB | 29924 | 89995;89996;89997 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| N2A | 28997 | 87214;87215;87216 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| N2B | 22500 | 67723;67724;67725 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| Novex-1 | 22625 | 68098;68099;68100 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| Novex-2 | 22692 | 68299;68300;68301 | chr2:178546735;178546734;178546733 | chr2:179411462;179411461;179411460 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/P | None | None | 0.998 | N | 0.659 | 0.301 | 0.238705975628 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 1.01626E-03 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | rs1354829063  |
-0.562 | 0.998 | N | 0.693 | 0.384 | 0.697601327402 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/Y | rs1354829063 |
-0.562 | 0.998 | N | 0.693 | 0.384 | 0.697601327402 | gnomAD-4.0.0 | 1.09474E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.43917E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0781 | likely_benign | 0.0795 | benign | -0.402 | Destabilizing | 0.91 | D | 0.455 | neutral | N | 0.481022066 | None | None | I |
| S/C | 0.1494 | likely_benign | 0.1599 | benign | -0.382 | Destabilizing | 1.0 | D | 0.647 | neutral | N | 0.480362141 | None | None | I |
| S/D | 0.6721 | likely_pathogenic | 0.6784 | pathogenic | 0.231 | Stabilizing | 0.985 | D | 0.515 | neutral | None | None | None | None | I |
| S/E | 0.7077 | likely_pathogenic | 0.7239 | pathogenic | 0.161 | Stabilizing | 0.985 | D | 0.519 | neutral | None | None | None | None | I |
| S/F | 0.3822 | ambiguous | 0.4048 | ambiguous | -0.88 | Destabilizing | 0.989 | D | 0.691 | prob.neutral | N | 0.513038484 | None | None | I |
| S/G | 0.0899 | likely_benign | 0.0928 | benign | -0.55 | Destabilizing | 0.985 | D | 0.476 | neutral | None | None | None | None | I |
| S/H | 0.4893 | ambiguous | 0.5142 | ambiguous | -0.972 | Destabilizing | 1.0 | D | 0.642 | neutral | None | None | None | None | I |
| S/I | 0.277 | likely_benign | 0.2932 | benign | -0.141 | Destabilizing | 0.942 | D | 0.579 | neutral | None | None | None | None | I |
| S/K | 0.7751 | likely_pathogenic | 0.796 | pathogenic | -0.524 | Destabilizing | 0.97 | D | 0.522 | neutral | None | None | None | None | I |
| S/L | 0.119 | likely_benign | 0.1244 | benign | -0.141 | Destabilizing | 0.092 | N | 0.361 | neutral | None | None | None | None | I |
| S/M | 0.2085 | likely_benign | 0.2134 | benign | -0.064 | Destabilizing | 0.991 | D | 0.664 | neutral | None | None | None | None | I |
| S/N | 0.1587 | likely_benign | 0.1557 | benign | -0.322 | Destabilizing | 0.985 | D | 0.534 | neutral | None | None | None | None | I |
| S/P | 0.1092 | likely_benign | 0.1115 | benign | -0.197 | Destabilizing | 0.998 | D | 0.659 | neutral | N | 0.443693042 | None | None | I |
| S/Q | 0.5325 | ambiguous | 0.5517 | ambiguous | -0.506 | Destabilizing | 0.999 | D | 0.588 | neutral | None | None | None | None | I |
| S/R | 0.7412 | likely_pathogenic | 0.7747 | pathogenic | -0.329 | Destabilizing | 0.996 | D | 0.655 | neutral | None | None | None | None | I |
| S/T | 0.0816 | likely_benign | 0.0784 | benign | -0.403 | Destabilizing | 0.122 | N | 0.174 | neutral | N | 0.432190756 | None | None | I |
| S/V | 0.2462 | likely_benign | 0.2575 | benign | -0.197 | Destabilizing | 0.942 | D | 0.555 | neutral | None | None | None | None | I |
| S/W | 0.5374 | ambiguous | 0.5656 | pathogenic | -0.897 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| S/Y | 0.3525 | ambiguous | 0.3746 | ambiguous | -0.614 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | N | 0.491883031 | 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.