Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30156 | 90691;90692;90693 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| N2AB | 28515 | 85768;85769;85770 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| N2A | 27588 | 82987;82988;82989 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| N2B | 21091 | 63496;63497;63498 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| Novex-1 | 21216 | 63871;63872;63873 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| Novex-2 | 21283 | 64072;64073;64074 | chr2:178552434;178552433;178552432 | chr2:179417161;179417160;179417159 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/E | rs762340648  |
0.621 | 0.999 | N | 0.583 | 0.402 | 0.406531046227 | gnomAD-2.1.1 | 4.11E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| K/E | rs762340648 |
0.621 | 0.999 | N | 0.583 | 0.402 | 0.406531046227 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/E | rs762340648 |
0.621 | 0.999 | N | 0.583 | 0.402 | 0.406531046227 | gnomAD-4.0.0 | 2.60206E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.8846E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.4587 | ambiguous | 0.4304 | ambiguous | -0.093 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| K/C | 0.7115 | likely_pathogenic | 0.6883 | pathogenic | -0.689 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| K/D | 0.818 | likely_pathogenic | 0.7945 | pathogenic | -0.477 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| K/E | 0.3178 | likely_benign | 0.3073 | benign | -0.488 | Destabilizing | 0.999 | D | 0.583 | neutral | N | 0.484764165 | None | None | I |
| K/F | 0.788 | likely_pathogenic | 0.7598 | pathogenic | -0.482 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| K/G | 0.6669 | likely_pathogenic | 0.6505 | pathogenic | -0.194 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| K/H | 0.3424 | ambiguous | 0.3086 | benign | -0.215 | Destabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | I |
| K/I | 0.3639 | ambiguous | 0.3403 | ambiguous | 0.095 | Stabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| K/L | 0.4499 | ambiguous | 0.4336 | ambiguous | 0.095 | Stabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| K/M | 0.2825 | likely_benign | 0.2831 | benign | -0.356 | Destabilizing | 1.0 | D | 0.643 | neutral | D | 0.532598184 | None | None | I |
| K/N | 0.6327 | likely_pathogenic | 0.5845 | pathogenic | -0.266 | Destabilizing | 1.0 | D | 0.657 | neutral | N | 0.511433478 | None | None | I |
| K/P | 0.9794 | likely_pathogenic | 0.9732 | pathogenic | 0.053 | Stabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| K/Q | 0.1757 | likely_benign | 0.168 | benign | -0.368 | Destabilizing | 1.0 | D | 0.646 | neutral | N | 0.482092006 | None | None | I |
| K/R | 0.079 | likely_benign | 0.0798 | benign | -0.217 | Destabilizing | 0.999 | D | 0.537 | neutral | N | 0.50471815 | None | None | I |
| K/S | 0.5342 | ambiguous | 0.4994 | ambiguous | -0.567 | Destabilizing | 0.999 | D | 0.617 | neutral | None | None | None | None | I |
| K/T | 0.2109 | likely_benign | 0.202 | benign | -0.472 | Destabilizing | 1.0 | D | 0.646 | neutral | N | 0.472971091 | None | None | I |
| K/V | 0.3613 | ambiguous | 0.3449 | ambiguous | 0.053 | Stabilizing | 1.0 | D | 0.627 | neutral | None | None | None | None | I |
| K/W | 0.7762 | likely_pathogenic | 0.7736 | pathogenic | -0.62 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | I |
| K/Y | 0.6746 | likely_pathogenic | 0.6455 | pathogenic | -0.278 | Destabilizing | 1.0 | D | 0.638 | 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.