Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35309 | 106150;106151;106152 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| N2AB | 33668 | 101227;101228;101229 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| N2A | 32741 | 98446;98447;98448 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| N2B | 26244 | 78955;78956;78957 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| Novex-1 | 26369 | 79330;79331;79332 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| Novex-2 | 26436 | 79531;79532;79533 | chr2:178530690;178530689;178530688 | chr2:179395417;179395416;179395415 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs558833547  |
-0.142 | 0.999 | N | 0.748 | 0.348 | 0.332646915603 | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| S/R | rs558833547 |
-0.142 | 0.999 | N | 0.748 | 0.348 | 0.332646915603 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| S/T | None | None | 0.997 | D | 0.535 | 0.297 | 0.340753184043 | gnomAD-4.0.0 | 1.59092E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85758E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1042 | likely_benign | 0.123 | benign | -0.232 | Destabilizing | 0.994 | D | 0.479 | neutral | None | None | None | None | I |
| S/C | 0.2118 | likely_benign | 0.2552 | benign | -0.314 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.491973434 | None | None | I |
| S/D | 0.3006 | likely_benign | 0.3832 | ambiguous | 0.289 | Stabilizing | 0.998 | D | 0.706 | prob.neutral | None | None | None | None | I |
| S/E | 0.5133 | ambiguous | 0.6332 | pathogenic | 0.185 | Stabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | I |
| S/F | 0.3434 | ambiguous | 0.4427 | ambiguous | -0.882 | Destabilizing | 0.999 | D | 0.767 | deleterious | None | None | None | None | I |
| S/G | 0.1022 | likely_benign | 0.1256 | benign | -0.311 | Destabilizing | 0.997 | D | 0.524 | neutral | N | 0.3858126 | None | None | I |
| S/H | 0.4586 | ambiguous | 0.5677 | pathogenic | -0.799 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| S/I | 0.3709 | ambiguous | 0.4817 | ambiguous | -0.161 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | N | 0.503240834 | None | None | I |
| S/K | 0.7383 | likely_pathogenic | 0.8434 | pathogenic | -0.378 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | None | None | None | None | I |
| S/L | 0.1938 | likely_benign | 0.2509 | benign | -0.161 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | I |
| S/M | 0.3641 | ambiguous | 0.4401 | ambiguous | -0.042 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| S/N | 0.1371 | likely_benign | 0.1906 | benign | -0.132 | Destabilizing | 0.997 | D | 0.685 | prob.neutral | N | 0.5172233 | None | None | I |
| S/P | 0.1632 | likely_benign | 0.3184 | benign | -0.157 | Destabilizing | 0.999 | D | 0.746 | deleterious | None | None | None | None | I |
| S/Q | 0.6127 | likely_pathogenic | 0.7367 | pathogenic | -0.362 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | I |
| S/R | 0.6694 | likely_pathogenic | 0.8048 | pathogenic | -0.216 | Destabilizing | 0.999 | D | 0.748 | deleterious | N | 0.510836045 | None | None | I |
| S/T | 0.1097 | likely_benign | 0.1294 | benign | -0.246 | Destabilizing | 0.997 | D | 0.535 | neutral | D | 0.532480754 | None | None | I |
| S/V | 0.3403 | ambiguous | 0.4361 | ambiguous | -0.157 | Destabilizing | 0.999 | D | 0.757 | deleterious | None | None | None | None | I |
| S/W | 0.5028 | ambiguous | 0.598 | pathogenic | -0.92 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| S/Y | 0.257 | likely_benign | 0.3214 | benign | -0.621 | Destabilizing | 0.999 | D | 0.754 | deleterious | 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.