Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1168 | 3727;3728;3729 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| N2AB | 1168 | 3727;3728;3729 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| N2A | 1168 | 3727;3728;3729 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| N2B | 1122 | 3589;3590;3591 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| Novex-1 | 1122 | 3589;3590;3591 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| Novex-2 | 1122 | 3589;3590;3591 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
| Novex-3 | 1168 | 3727;3728;3729 | chr2:178781142;178781141;178781140 | chr2:179645869;179645868;179645867 |
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/P | rs1488930199  |
None | 0.984 | D | 0.711 | 0.561 | None | 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 |
| S/P | rs1488930199 |
None | 0.984 | D | 0.711 | 0.561 | None | gnomAD-4.0.0 | 4.05949E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.81958E-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 | 0.0927 | likely_benign | 0.0928 | benign | -0.549 | Destabilizing | 0.026 | N | 0.334 | neutral | N | 0.513354809 | None | None | I |
| S/C | 0.2334 | likely_benign | 0.2378 | benign | -0.404 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | D | 0.578337718 | None | None | I |
| S/D | 0.7651 | likely_pathogenic | 0.776 | pathogenic | 0.119 | Stabilizing | 0.919 | D | 0.56 | neutral | None | None | None | None | I |
| S/E | 0.7399 | likely_pathogenic | 0.7509 | pathogenic | 0.059 | Stabilizing | 0.919 | D | 0.555 | neutral | None | None | None | None | I |
| S/F | 0.3154 | likely_benign | 0.3236 | benign | -0.992 | Destabilizing | 0.984 | D | 0.781 | deleterious | N | 0.507753892 | None | None | I |
| S/G | 0.174 | likely_benign | 0.1897 | benign | -0.717 | Destabilizing | 0.851 | D | 0.553 | neutral | None | None | None | None | I |
| S/H | 0.5453 | ambiguous | 0.5667 | pathogenic | -1.247 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/I | 0.2818 | likely_benign | 0.2796 | benign | -0.228 | Destabilizing | 0.976 | D | 0.771 | deleterious | None | None | None | None | I |
| S/K | 0.7831 | likely_pathogenic | 0.8019 | pathogenic | -0.521 | Destabilizing | 0.919 | D | 0.559 | neutral | None | None | None | None | I |
| S/L | 0.1662 | likely_benign | 0.1706 | benign | -0.228 | Destabilizing | 0.851 | D | 0.695 | prob.neutral | None | None | None | None | I |
| S/M | 0.3016 | likely_benign | 0.3035 | benign | 0.032 | Stabilizing | 0.999 | D | 0.698 | prob.neutral | None | None | None | None | I |
| S/N | 0.3292 | likely_benign | 0.3342 | benign | -0.333 | Destabilizing | 0.919 | D | 0.584 | neutral | None | None | None | None | I |
| S/P | 0.7035 | likely_pathogenic | 0.749 | pathogenic | -0.304 | Destabilizing | 0.984 | D | 0.711 | prob.delet. | D | 0.559728801 | None | None | I |
| S/Q | 0.6558 | likely_pathogenic | 0.6758 | pathogenic | -0.562 | Destabilizing | 0.988 | D | 0.597 | neutral | None | None | None | None | I |
| S/R | 0.7143 | likely_pathogenic | 0.7375 | pathogenic | -0.368 | Destabilizing | 0.988 | D | 0.713 | prob.delet. | None | None | None | None | I |
| S/T | 0.0794 | likely_benign | 0.0797 | benign | -0.424 | Destabilizing | 0.103 | N | 0.391 | neutral | N | 0.458068216 | None | None | I |
| S/V | 0.2139 | likely_benign | 0.2135 | benign | -0.304 | Destabilizing | 0.851 | D | 0.703 | prob.neutral | None | None | None | None | I |
| S/W | 0.6089 | likely_pathogenic | 0.6363 | pathogenic | -0.95 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | I |
| S/Y | 0.3519 | ambiguous | 0.3623 | ambiguous | -0.681 | Destabilizing | 0.995 | D | 0.781 | deleterious | D | 0.568617002 | 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.