Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| N2AB | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| N2A | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| N2B | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| Novex-1 | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| Novex-2 | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
| Novex-3 | 192 | 799;800;801 | chr2:178800404;178800403;178800402 | chr2:179665131;179665130;179665129 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | None | None | 0.343 | N | 0.609 | 0.186 | 0.689481310135 | gnomAD-4.0.0 | 6.84072E-07 | None | None | None | -0.43(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99306E-07 | 0 | 0 |
| L/R | rs1375853157  |
None | 0.779 | N | 0.729 | 0.408 | 0.782842511238 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.603(TCAP) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/R | rs1375853157 |
None | 0.779 | N | 0.729 | 0.408 | 0.782842511238 | gnomAD-4.0.0 | 2.56104E-06 | None | None | None | -0.603(TCAP) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.7835E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.354 | ambiguous | 0.4739 | ambiguous | -1.362 | Destabilizing | 0.452 | N | 0.561 | neutral | None | None | None | -0.375(TCAP) | N |
| L/C | 0.8245 | likely_pathogenic | 0.8691 | pathogenic | -0.93 | Destabilizing | 0.978 | D | 0.647 | neutral | None | None | None | -0.412(TCAP) | N |
| L/D | 0.827 | likely_pathogenic | 0.8881 | pathogenic | -0.519 | Destabilizing | 0.853 | D | 0.746 | deleterious | None | None | None | -0.39(TCAP) | N |
| L/E | 0.457 | ambiguous | 0.5543 | ambiguous | -0.543 | Destabilizing | 0.81 | D | 0.753 | deleterious | None | None | None | -0.508(TCAP) | N |
| L/F | 0.2392 | likely_benign | 0.3346 | benign | -0.977 | Destabilizing | 0.697 | D | 0.605 | neutral | None | None | None | -0.206(TCAP) | N |
| L/G | 0.8117 | likely_pathogenic | 0.8931 | pathogenic | -1.643 | Destabilizing | 0.853 | D | 0.729 | prob.delet. | None | None | None | -0.311(TCAP) | N |
| L/H | 0.3112 | likely_benign | 0.4368 | ambiguous | -0.8 | Destabilizing | 0.982 | D | 0.732 | prob.delet. | None | None | None | 0.302(TCAP) | N |
| L/I | 0.1145 | likely_benign | 0.1369 | benign | -0.689 | Destabilizing | 0.008 | N | 0.467 | neutral | None | None | None | -0.599(TCAP) | N |
| L/K | 0.3094 | likely_benign | 0.3917 | ambiguous | -0.782 | Destabilizing | 0.146 | N | 0.715 | prob.delet. | None | None | None | -0.627(TCAP) | N |
| L/M | 0.1689 | likely_benign | 0.2051 | benign | -0.58 | Destabilizing | 0.343 | N | 0.609 | neutral | N | 0.49887892 | None | -0.43(TCAP) | N |
| L/N | 0.5519 | ambiguous | 0.6711 | pathogenic | -0.583 | Destabilizing | 0.853 | D | 0.751 | deleterious | None | None | None | -0.494(TCAP) | N |
| L/P | 0.9625 | likely_pathogenic | 0.9831 | pathogenic | -0.88 | Destabilizing | 0.899 | D | 0.753 | deleterious | D | 0.568686662 | None | -0.52(TCAP) | N |
| L/Q | 0.1816 | likely_benign | 0.2609 | benign | -0.789 | Destabilizing | 0.786 | D | 0.727 | prob.delet. | N | 0.464170041 | None | -0.49(TCAP) | N |
| L/R | 0.2255 | likely_benign | 0.3111 | benign | -0.212 | Destabilizing | 0.779 | D | 0.729 | prob.delet. | N | 0.470216411 | None | -0.603(TCAP) | N |
| L/S | 0.4268 | ambiguous | 0.5866 | pathogenic | -1.231 | Destabilizing | 0.743 | D | 0.624 | neutral | None | None | None | -0.186(TCAP) | N |
| L/T | 0.2438 | likely_benign | 0.3371 | benign | -1.139 | Destabilizing | 0.015 | N | 0.381 | neutral | None | None | None | -0.3(TCAP) | N |
| L/V | 0.108 | likely_benign | 0.1248 | benign | -0.88 | Destabilizing | None | N | 0.319 | neutral | N | 0.46687838 | None | -0.52(TCAP) | N |
| L/W | 0.4533 | ambiguous | 0.5782 | pathogenic | -0.975 | Destabilizing | 0.995 | D | 0.74 | deleterious | None | None | None | -0.334(TCAP) | N |
| L/Y | 0.528 | ambiguous | 0.6564 | pathogenic | -0.749 | Destabilizing | 0.354 | N | 0.68 | prob.neutral | None | None | None | -0.245(TCAP) | 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.