Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28429 | 85510;85511;85512 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| N2AB | 26788 | 80587;80588;80589 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| N2A | 25861 | 77806;77807;77808 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| N2B | 19364 | 58315;58316;58317 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| Novex-1 | 19489 | 58690;58691;58692 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| Novex-2 | 19556 | 58891;58892;58893 | chr2:178560847;178560846;178560845 | chr2:179425574;179425573;179425572 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | rs747216991  |
-1.229 | 0.124 | N | 0.638 | 0.278 | 0.534093007224 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 5.81E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/E | rs747216991 |
-1.229 | 0.124 | N | 0.638 | 0.278 | 0.534093007224 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.30993E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/E | rs747216991 |
-1.229 | 0.124 | N | 0.638 | 0.278 | 0.534093007224 | gnomAD-4.0.0 | 7.68748E-06 | None | None | None | None | I | None | 0 | 1.01716E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2717 | likely_benign | 0.3065 | benign | -1.805 | Destabilizing | 0.055 | N | 0.517 | neutral | N | 0.498497814 | None | None | I |
| V/C | 0.6903 | likely_pathogenic | 0.6947 | pathogenic | -1.678 | Destabilizing | 0.909 | D | 0.639 | neutral | None | None | None | None | I |
| V/D | 0.4919 | ambiguous | 0.5493 | ambiguous | -1.959 | Destabilizing | 0.567 | D | 0.722 | prob.delet. | None | None | None | None | I |
| V/E | 0.3355 | likely_benign | 0.3691 | ambiguous | -1.774 | Destabilizing | 0.124 | N | 0.638 | neutral | N | 0.46896434 | None | None | I |
| V/F | 0.1971 | likely_benign | 0.2104 | benign | -1.116 | Destabilizing | 0.567 | D | 0.629 | neutral | None | None | None | None | I |
| V/G | 0.3395 | likely_benign | 0.3655 | ambiguous | -2.309 | Highly Destabilizing | 0.497 | N | 0.68 | prob.neutral | N | 0.460060207 | None | None | I |
| V/H | 0.5806 | likely_pathogenic | 0.6098 | pathogenic | -2.025 | Highly Destabilizing | 0.909 | D | 0.758 | deleterious | None | None | None | None | I |
| V/I | 0.0753 | likely_benign | 0.0764 | benign | -0.426 | Destabilizing | 0.001 | N | 0.405 | neutral | N | 0.438449432 | None | None | I |
| V/K | 0.3826 | ambiguous | 0.4371 | ambiguous | -1.366 | Destabilizing | 0.396 | N | 0.645 | neutral | None | None | None | None | I |
| V/L | 0.1972 | likely_benign | 0.2206 | benign | -0.426 | Destabilizing | 0.02 | N | 0.519 | neutral | N | 0.512523117 | None | None | I |
| V/M | 0.1434 | likely_benign | 0.1587 | benign | -0.69 | Destabilizing | 0.567 | D | 0.499 | neutral | None | None | None | None | I |
| V/N | 0.3226 | likely_benign | 0.3542 | ambiguous | -1.6 | Destabilizing | 0.567 | D | 0.733 | prob.delet. | None | None | None | None | I |
| V/P | 0.9714 | likely_pathogenic | 0.9713 | pathogenic | -0.855 | Destabilizing | 0.726 | D | 0.698 | prob.neutral | None | None | None | None | I |
| V/Q | 0.3379 | likely_benign | 0.3767 | ambiguous | -1.482 | Destabilizing | 0.011 | N | 0.592 | neutral | None | None | None | None | I |
| V/R | 0.3227 | likely_benign | 0.3712 | ambiguous | -1.25 | Destabilizing | 0.396 | N | 0.733 | prob.delet. | None | None | None | None | I |
| V/S | 0.2564 | likely_benign | 0.2807 | benign | -2.291 | Highly Destabilizing | 0.157 | N | 0.621 | neutral | None | None | None | None | I |
| V/T | 0.1725 | likely_benign | 0.1924 | benign | -1.956 | Destabilizing | 0.001 | N | 0.418 | neutral | None | None | None | None | I |
| V/W | 0.8329 | likely_pathogenic | 0.8449 | pathogenic | -1.516 | Destabilizing | 0.968 | D | 0.765 | deleterious | None | None | None | None | I |
| V/Y | 0.5177 | ambiguous | 0.5369 | ambiguous | -1.12 | Destabilizing | 0.726 | D | 0.631 | 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.