Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23957 | 72094;72095;72096 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| N2AB | 22316 | 67171;67172;67173 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| N2A | 21389 | 64390;64391;64392 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| N2B | 14892 | 44899;44900;44901 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| Novex-1 | 15017 | 45274;45275;45276 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| Novex-2 | 15084 | 45475;45476;45477 | chr2:178574263;178574262;178574261 | chr2:179438990;179438989;179438988 |
| 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 | None | None | 1.0 | N | 0.803 | 0.566 | 0.464098490096 | gnomAD-4.0.0 | 6.8468E-07 | None | None | None | None | I | None | 2.99097E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/N | None | None | 1.0 | N | 0.713 | 0.496 | 0.452640719197 | gnomAD-4.0.0 | 6.8468E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00025E-07 | 0 | 0 |
| T/S | rs1330924504  |
-0.572 | 0.999 | N | 0.519 | 0.467 | 0.355865052028 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/S | rs1330924504 |
-0.572 | 0.999 | N | 0.519 | 0.467 | 0.355865052028 | gnomAD-4.0.0 | 1.36936E-06 | None | None | None | None | I | None | 2.99097E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15974E-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 | 0.1529 | likely_benign | 0.1771 | benign | -0.857 | Destabilizing | 0.999 | D | 0.533 | neutral | N | 0.485032949 | None | None | I |
| T/C | 0.6791 | likely_pathogenic | 0.7123 | pathogenic | -0.525 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| T/D | 0.7716 | likely_pathogenic | 0.8193 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| T/E | 0.7051 | likely_pathogenic | 0.755 | pathogenic | -0.359 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | I |
| T/F | 0.5539 | ambiguous | 0.617 | pathogenic | -0.984 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | None | I |
| T/G | 0.4811 | ambiguous | 0.5337 | ambiguous | -1.095 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| T/H | 0.6302 | likely_pathogenic | 0.6656 | pathogenic | -1.378 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| T/I | 0.2366 | likely_benign | 0.2664 | benign | -0.316 | Destabilizing | 1.0 | D | 0.803 | deleterious | N | 0.509171459 | None | None | I |
| T/K | 0.5995 | likely_pathogenic | 0.6599 | pathogenic | -0.721 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | I |
| T/L | 0.1783 | likely_benign | 0.1985 | benign | -0.316 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| T/M | 0.1466 | likely_benign | 0.1726 | benign | 0.088 | Stabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| T/N | 0.2562 | likely_benign | 0.2954 | benign | -0.631 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | N | 0.506277529 | None | None | I |
| T/P | 0.4649 | ambiguous | 0.5337 | ambiguous | -0.465 | Destabilizing | 1.0 | D | 0.791 | deleterious | D | 0.525649232 | None | None | I |
| T/Q | 0.5255 | ambiguous | 0.5651 | pathogenic | -0.879 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| T/R | 0.5595 | ambiguous | 0.6203 | pathogenic | -0.434 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | I |
| T/S | 0.1914 | likely_benign | 0.2216 | benign | -0.924 | Destabilizing | 0.999 | D | 0.519 | neutral | N | 0.476612705 | None | None | I |
| T/V | 0.1892 | likely_benign | 0.21 | benign | -0.465 | Destabilizing | 0.999 | D | 0.578 | neutral | None | None | None | None | I |
| T/W | 0.9028 | likely_pathogenic | 0.9222 | pathogenic | -0.877 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| T/Y | 0.6652 | likely_pathogenic | 0.6988 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.841 | deleterious | 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.