Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33174 | 99745;99746;99747 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| N2AB | 31533 | 94822;94823;94824 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| N2A | 30606 | 92041;92042;92043 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| N2B | 24109 | 72550;72551;72552 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| Novex-1 | 24234 | 72925;72926;72927 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| Novex-2 | 24301 | 73126;73127;73128 | chr2:178537687;178537686;178537685 | chr2:179402414;179402413;179402412 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs879116103  |
-2.194 | None | N | 0.277 | 0.086 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 0 |
| I/T | rs879116103 |
-2.194 | None | N | 0.277 | 0.086 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs879116103 |
-2.194 | None | N | 0.277 | 0.086 | None | gnomAD-4.0.0 | 6.197E-06 | None | None | None | None | N | None | 5.3396E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08571E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.211 | likely_benign | 0.206 | benign | -2.358 | Highly Destabilizing | 0.019 | N | 0.369 | neutral | None | None | None | None | N |
| I/C | 0.5799 | likely_pathogenic | 0.5595 | ambiguous | -1.526 | Destabilizing | 0.605 | D | 0.517 | neutral | None | None | None | None | N |
| I/D | 0.7997 | likely_pathogenic | 0.8065 | pathogenic | -2.601 | Highly Destabilizing | 0.177 | N | 0.569 | neutral | None | None | None | None | N |
| I/E | 0.5057 | ambiguous | 0.4962 | ambiguous | -2.47 | Highly Destabilizing | 0.032 | N | 0.522 | neutral | None | None | None | None | N |
| I/F | 0.1574 | likely_benign | 0.186 | benign | -1.437 | Destabilizing | 0.079 | N | 0.546 | neutral | None | None | None | None | N |
| I/G | 0.6264 | likely_pathogenic | 0.6359 | pathogenic | -2.81 | Highly Destabilizing | 0.082 | N | 0.518 | neutral | None | None | None | None | N |
| I/H | 0.3713 | ambiguous | 0.3628 | ambiguous | -2.205 | Highly Destabilizing | 0.66 | D | 0.582 | neutral | None | None | None | None | N |
| I/K | 0.201 | likely_benign | 0.1784 | benign | -1.764 | Destabilizing | None | N | 0.479 | neutral | N | 0.444493623 | None | None | N |
| I/L | 0.1107 | likely_benign | 0.1133 | benign | -1.092 | Destabilizing | None | N | 0.331 | neutral | N | 0.497021386 | None | None | N |
| I/M | 0.0793 | likely_benign | 0.089 | benign | -0.933 | Destabilizing | None | N | 0.281 | neutral | N | 0.513876351 | None | None | N |
| I/N | 0.3172 | likely_benign | 0.3251 | benign | -1.836 | Destabilizing | 0.177 | N | 0.551 | neutral | None | None | None | None | N |
| I/P | 0.9819 | likely_pathogenic | 0.9833 | pathogenic | -1.492 | Destabilizing | 0.304 | N | 0.584 | neutral | None | None | None | None | N |
| I/Q | 0.2796 | likely_benign | 0.2574 | benign | -1.862 | Destabilizing | 0.082 | N | 0.583 | neutral | None | None | None | None | N |
| I/R | 0.1508 | likely_benign | 0.1382 | benign | -1.292 | Destabilizing | None | N | 0.499 | neutral | N | 0.452171744 | None | None | N |
| I/S | 0.234 | likely_benign | 0.2297 | benign | -2.458 | Highly Destabilizing | 0.043 | N | 0.53 | neutral | None | None | None | None | N |
| I/T | 0.1178 | likely_benign | 0.123 | benign | -2.21 | Highly Destabilizing | None | N | 0.277 | neutral | N | 0.463407458 | None | None | N |
| I/V | 0.0657 | likely_benign | 0.0635 | benign | -1.492 | Destabilizing | None | N | 0.154 | neutral | N | 0.421387477 | None | None | N |
| I/W | 0.7151 | likely_pathogenic | 0.7723 | pathogenic | -1.773 | Destabilizing | 0.963 | D | 0.59 | neutral | None | None | None | None | N |
| I/Y | 0.5024 | ambiguous | 0.5187 | ambiguous | -1.527 | Destabilizing | 0.02 | N | 0.55 | neutral | None | None | None | None | 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.