Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8953 | 27082;27083;27084 | chr2:178713277;178713276;178713275 | chr2:179578004;179578003;179578002 |
| N2AB | 8636 | 26131;26132;26133 | chr2:178713277;178713276;178713275 | chr2:179578004;179578003;179578002 |
| N2A | 7709 | 23350;23351;23352 | chr2:178713277;178713276;178713275 | chr2:179578004;179578003;179578002 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1195723456  |
None | 0.98 | D | 0.531 | 0.625 | 0.862594239932 | gnomAD-4.0.0 | 1.60145E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.45033E-05 | 0 |
| P/S | rs756003188 |
-0.289 | 0.659 | D | 0.235 | 0.515 | 0.429203605099 | gnomAD-2.1.1 | 3.75E-05 | None | None | None | None | I | None | 0 | 1.19624E-04 | None | 1.01626E-04 | 0 | None | 0 | None | 4.72E-05 | 2.78E-05 | 0 |
| P/S | rs756003188 |
-0.289 | 0.659 | D | 0.235 | 0.515 | 0.429203605099 | gnomAD-3.1.2 | 9.2E-05 | None | None | None | None | I | None | 0 | 5.89468E-04 | 0 | 0 | 0 | None | 2.82912E-04 | 0 | 2.94E-05 | 0 | 0 |
| P/S | rs756003188 |
-0.289 | 0.659 | D | 0.235 | 0.515 | 0.429203605099 | gnomAD-4.0.0 | 2.29953E-05 | None | None | None | None | I | None | 0 | 2.36048E-04 | None | 0 | 0 | None | 1.25372E-04 | 0 | 1.27403E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0909 | likely_benign | 0.0973 | benign | -0.388 | Destabilizing | 0.4 | N | 0.248 | neutral | D | 0.545326645 | None | None | I |
| P/C | 0.6406 | likely_pathogenic | 0.6507 | pathogenic | -0.799 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | I |
| P/D | 0.6155 | likely_pathogenic | 0.6287 | pathogenic | -0.409 | Destabilizing | 0.985 | D | 0.406 | neutral | None | None | None | None | I |
| P/E | 0.3718 | ambiguous | 0.3776 | ambiguous | -0.524 | Destabilizing | 0.971 | D | 0.423 | neutral | None | None | None | None | I |
| P/F | 0.4338 | ambiguous | 0.4673 | ambiguous | -0.736 | Destabilizing | 0.999 | D | 0.589 | neutral | None | None | None | None | I |
| P/G | 0.4023 | ambiguous | 0.4581 | ambiguous | -0.454 | Destabilizing | 0.985 | D | 0.46 | neutral | None | None | None | None | I |
| P/H | 0.2043 | likely_benign | 0.2158 | benign | -0.007 | Destabilizing | 0.999 | D | 0.511 | neutral | D | 0.612010596 | None | None | I |
| P/I | 0.3536 | ambiguous | 0.3635 | ambiguous | -0.355 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | I |
| P/K | 0.3522 | ambiguous | 0.3981 | ambiguous | -0.443 | Destabilizing | 0.971 | D | 0.443 | neutral | None | None | None | None | I |
| P/L | 0.1147 | likely_benign | 0.1275 | benign | -0.355 | Destabilizing | 0.98 | D | 0.531 | neutral | D | 0.616421724 | None | None | I |
| P/M | 0.3211 | likely_benign | 0.3332 | benign | -0.604 | Destabilizing | 1.0 | D | 0.511 | neutral | None | None | None | None | I |
| P/N | 0.4358 | ambiguous | 0.4598 | ambiguous | -0.245 | Destabilizing | 0.996 | D | 0.496 | neutral | None | None | None | None | I |
| P/Q | 0.1786 | likely_benign | 0.183 | benign | -0.463 | Destabilizing | 0.856 | D | 0.343 | neutral | None | None | None | None | I |
| P/R | 0.2212 | likely_benign | 0.2566 | benign | 0.034 | Stabilizing | 0.994 | D | 0.497 | neutral | D | 0.627858513 | None | None | I |
| P/S | 0.1207 | likely_benign | 0.1334 | benign | -0.548 | Destabilizing | 0.659 | D | 0.235 | neutral | D | 0.557821812 | None | None | I |
| P/T | 0.1414 | likely_benign | 0.1531 | benign | -0.572 | Destabilizing | 0.961 | D | 0.444 | neutral | D | 0.637145099 | None | None | I |
| P/V | 0.2436 | likely_benign | 0.2514 | benign | -0.338 | Destabilizing | 0.996 | D | 0.444 | neutral | None | None | None | None | I |
| P/W | 0.6746 | likely_pathogenic | 0.708 | pathogenic | -0.789 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| P/Y | 0.4322 | ambiguous | 0.4591 | ambiguous | -0.521 | Destabilizing | 0.999 | D | 0.587 | neutral | 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.