Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1172 | 3739;3740;3741 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| N2AB | 1172 | 3739;3740;3741 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| N2A | 1172 | 3739;3740;3741 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| N2B | 1126 | 3601;3602;3603 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| Novex-1 | 1126 | 3601;3602;3603 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| Novex-2 | 1126 | 3601;3602;3603 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
| Novex-3 | 1172 | 3739;3740;3741 | chr2:178781130;178781129;178781128 | chr2:179645857;179645856;179645855 |
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/I | rs375735354  |
-0.005 | 0.992 | N | 0.518 | 0.156 | None | gnomAD-2.1.1 | 3.59E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.94E-05 | 0 |
| L/I | rs375735354 |
-0.005 | 0.992 | N | 0.518 | 0.156 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17578E-04 | 0 | 0 |
| L/I | rs375735354 |
-0.005 | 0.992 | N | 0.518 | 0.156 | None | gnomAD-4.0.0 | 5.94861E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.05127E-05 | 0 | 1.60056E-05 |
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 | 0.6531 | likely_pathogenic | 0.6324 | pathogenic | -0.991 | Destabilizing | 0.997 | D | 0.66 | neutral | None | None | None | None | I |
| L/C | 0.862 | likely_pathogenic | 0.8363 | pathogenic | -0.73 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| L/D | 0.9778 | likely_pathogenic | 0.9758 | pathogenic | -0.144 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| L/E | 0.8124 | likely_pathogenic | 0.8011 | pathogenic | -0.175 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| L/F | 0.4317 | ambiguous | 0.4147 | ambiguous | -0.645 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | N | 0.507489308 | None | None | I |
| L/G | 0.9076 | likely_pathogenic | 0.9024 | pathogenic | -1.246 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | I |
| L/H | 0.7079 | likely_pathogenic | 0.6885 | pathogenic | -0.408 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | D | 0.535935038 | None | None | I |
| L/I | 0.2955 | likely_benign | 0.2751 | benign | -0.403 | Destabilizing | 0.992 | D | 0.518 | neutral | N | 0.475469109 | None | None | I |
| L/K | 0.6085 | likely_pathogenic | 0.5956 | pathogenic | -0.585 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | None | None | None | None | I |
| L/M | 0.2215 | likely_benign | 0.2085 | benign | -0.45 | Destabilizing | 0.985 | D | 0.426 | neutral | None | None | None | None | I |
| L/N | 0.907 | likely_pathogenic | 0.902 | pathogenic | -0.418 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| L/P | 0.9701 | likely_pathogenic | 0.9661 | pathogenic | -0.565 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.575879896 | None | None | I |
| L/Q | 0.4472 | ambiguous | 0.4286 | ambiguous | -0.573 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| L/R | 0.521 | ambiguous | 0.5073 | ambiguous | -0.06 | Destabilizing | 0.999 | D | 0.724 | prob.delet. | N | 0.50557758 | None | None | I |
| L/S | 0.7825 | likely_pathogenic | 0.7689 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| L/T | 0.6428 | likely_pathogenic | 0.6181 | pathogenic | -0.918 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| L/V | 0.2601 | likely_benign | 0.2386 | benign | -0.565 | Destabilizing | 0.992 | D | 0.539 | neutral | N | 0.483339823 | None | None | I |
| L/W | 0.6455 | likely_pathogenic | 0.6426 | pathogenic | -0.679 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| L/Y | 0.7674 | likely_pathogenic | 0.7516 | pathogenic | -0.444 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | 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.