Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30370 | 91333;91334;91335 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| N2AB | 28729 | 86410;86411;86412 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| N2A | 27802 | 83629;83630;83631 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| N2B | 21305 | 64138;64139;64140 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| Novex-1 | 21430 | 64513;64514;64515 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| Novex-2 | 21497 | 64714;64715;64716 | chr2:178551792;178551791;178551790 | chr2:179416519;179416518;179416517 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/F | rs876658092  |
-0.7 | 0.999 | N | 0.574 | 0.246 | 0.517655672 | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| L/F | rs876658092 |
-0.7 | 0.999 | N | 0.574 | 0.246 | 0.517655672 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| L/F | rs876658092 |
-0.7 | 0.999 | N | 0.574 | 0.246 | 0.517655672 | gnomAD-4.0.0 | 6.40576E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.57158E-06 | 1.34027E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.7015 | likely_pathogenic | 0.7035 | pathogenic | -0.861 | Destabilizing | 0.997 | D | 0.521 | neutral | None | None | None | None | I |
| L/C | 0.8153 | likely_pathogenic | 0.8187 | pathogenic | -0.688 | Destabilizing | 1.0 | D | 0.623 | neutral | None | None | None | None | I |
| L/D | 0.9721 | likely_pathogenic | 0.9724 | pathogenic | -0.329 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| L/E | 0.8695 | likely_pathogenic | 0.8678 | pathogenic | -0.383 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | I |
| L/F | 0.3271 | likely_benign | 0.3717 | ambiguous | -0.657 | Destabilizing | 0.999 | D | 0.574 | neutral | N | 0.47533203 | None | None | I |
| L/G | 0.8991 | likely_pathogenic | 0.8958 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | I |
| L/H | 0.5886 | likely_pathogenic | 0.5869 | pathogenic | -0.168 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | N | 0.509899391 | None | None | I |
| L/I | 0.1645 | likely_benign | 0.1741 | benign | -0.424 | Destabilizing | 0.992 | D | 0.473 | neutral | N | 0.51913495 | None | None | I |
| L/K | 0.7287 | likely_pathogenic | 0.7127 | pathogenic | -0.522 | Destabilizing | 1.0 | D | 0.607 | neutral | None | None | None | None | I |
| L/M | 0.1935 | likely_benign | 0.1959 | benign | -0.542 | Destabilizing | 0.985 | D | 0.436 | neutral | None | None | None | None | I |
| L/N | 0.8098 | likely_pathogenic | 0.7995 | pathogenic | -0.391 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| L/P | 0.9459 | likely_pathogenic | 0.9539 | pathogenic | -0.537 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.469545132 | None | None | I |
| L/Q | 0.4709 | ambiguous | 0.4525 | ambiguous | -0.579 | Destabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | I |
| L/R | 0.5482 | ambiguous | 0.5507 | ambiguous | 0.063 | Stabilizing | 0.999 | D | 0.644 | neutral | N | 0.474728025 | None | None | I |
| L/S | 0.7471 | likely_pathogenic | 0.7506 | pathogenic | -0.871 | Destabilizing | 1.0 | D | 0.613 | neutral | None | None | None | None | I |
| L/T | 0.6283 | likely_pathogenic | 0.63 | pathogenic | -0.814 | Destabilizing | 1.0 | D | 0.559 | neutral | None | None | None | None | I |
| L/V | 0.2123 | likely_benign | 0.2305 | benign | -0.537 | Destabilizing | 0.992 | D | 0.51 | neutral | N | 0.503434778 | None | None | I |
| L/W | 0.6133 | likely_pathogenic | 0.6418 | pathogenic | -0.675 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | I |
| L/Y | 0.6612 | likely_pathogenic | 0.6785 | pathogenic | -0.45 | Destabilizing | 1.0 | D | 0.609 | 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.