Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19564 | 58915;58916;58917 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| N2AB | 17923 | 53992;53993;53994 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| N2A | 16996 | 51211;51212;51213 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| N2B | 10499 | 31720;31721;31722 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| Novex-1 | 10624 | 32095;32096;32097 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| Novex-2 | 10691 | 32296;32297;32298 | chr2:178593610;178593609;178593608 | chr2:179458337;179458336;179458335 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1236959839  |
-0.475 | 0.17 | N | 0.268 | 0.092 | 0.101711395817 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.52742E-04 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs1236959839 |
-0.475 | 0.17 | N | 0.268 | 0.092 | 0.101711395817 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 0 | 0 | 0 |
| D/E | rs1236959839 |
-0.475 | 0.17 | N | 0.268 | 0.092 | 0.101711395817 | gnomAD-4.0.0 | 6.08982E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.27583E-04 | None | 0 | 0 | 4.81979E-06 | 0 | 0 |
| D/N | rs182400450 |
-0.81 | 0.046 | N | 0.231 | 0.174 | None | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs182400450 |
-0.81 | 0.046 | N | 0.231 | 0.174 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs182400450 |
-0.81 | 0.046 | N | 0.231 | 0.174 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs182400450 |
-0.81 | 0.046 | N | 0.231 | 0.174 | None | gnomAD-4.0.0 | 6.56961E-06 | None | None | None | None | I | None | 2.40512E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.999 | N | 0.772 | 0.305 | 0.36256342048 | gnomAD-4.0.0 | 3.18728E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41896E-04 | 2.86053E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2265 | likely_benign | 0.2017 | benign | -0.438 | Destabilizing | 0.939 | D | 0.608 | neutral | N | 0.498735461 | None | None | I |
| D/C | 0.7629 | likely_pathogenic | 0.7222 | pathogenic | -0.124 | Destabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | None | I |
| D/E | 0.1703 | likely_benign | 0.153 | benign | -0.494 | Destabilizing | 0.17 | N | 0.268 | neutral | N | 0.41338599 | None | None | I |
| D/F | 0.7296 | likely_pathogenic | 0.6842 | pathogenic | -0.336 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | I |
| D/G | 0.3154 | likely_benign | 0.286 | benign | -0.679 | Destabilizing | 0.885 | D | 0.523 | neutral | N | 0.462108712 | None | None | I |
| D/H | 0.4068 | ambiguous | 0.3602 | ambiguous | -0.412 | Destabilizing | 0.998 | D | 0.736 | prob.delet. | N | 0.473718507 | None | None | I |
| D/I | 0.4529 | ambiguous | 0.4134 | ambiguous | 0.162 | Stabilizing | 0.993 | D | 0.781 | deleterious | None | None | None | None | I |
| D/K | 0.3833 | ambiguous | 0.3734 | ambiguous | -0.211 | Destabilizing | 0.953 | D | 0.617 | neutral | None | None | None | None | I |
| D/L | 0.4578 | ambiguous | 0.4074 | ambiguous | 0.162 | Stabilizing | 0.993 | D | 0.785 | deleterious | None | None | None | None | I |
| D/M | 0.7058 | likely_pathogenic | 0.6493 | pathogenic | 0.422 | Stabilizing | 0.999 | D | 0.758 | deleterious | None | None | None | None | I |
| D/N | 0.1482 | likely_benign | 0.1325 | benign | -0.398 | Destabilizing | 0.046 | N | 0.231 | neutral | N | 0.50750966 | None | None | I |
| D/P | 0.5621 | ambiguous | 0.5295 | ambiguous | -0.015 | Destabilizing | 0.998 | D | 0.741 | deleterious | None | None | None | None | I |
| D/Q | 0.3929 | ambiguous | 0.3646 | ambiguous | -0.343 | Destabilizing | 0.986 | D | 0.661 | neutral | None | None | None | None | I |
| D/R | 0.4931 | ambiguous | 0.4662 | ambiguous | -0.012 | Destabilizing | 0.986 | D | 0.764 | deleterious | None | None | None | None | I |
| D/S | 0.1789 | likely_benign | 0.1552 | benign | -0.564 | Destabilizing | 0.91 | D | 0.468 | neutral | None | None | None | None | I |
| D/T | 0.3462 | ambiguous | 0.313 | benign | -0.386 | Destabilizing | 0.986 | D | 0.661 | neutral | None | None | None | None | I |
| D/V | 0.2792 | likely_benign | 0.2501 | benign | -0.015 | Destabilizing | 0.991 | D | 0.786 | deleterious | N | 0.464462115 | None | None | I |
| D/W | 0.931 | likely_pathogenic | 0.9195 | pathogenic | -0.216 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | I |
| D/Y | 0.3291 | likely_benign | 0.2978 | benign | -0.13 | Destabilizing | 0.999 | D | 0.772 | deleterious | N | 0.488606758 | 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.