Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25177 | 75754;75755;75756 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| N2AB | 23536 | 70831;70832;70833 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| N2A | 22609 | 68050;68051;68052 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| N2B | 16112 | 48559;48560;48561 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| Novex-1 | 16237 | 48934;48935;48936 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| Novex-2 | 16304 | 49135;49136;49137 | chr2:178570603;178570602;178570601 | chr2:179435330;179435329;179435328 |
| 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/I | rs552074847  |
0.084 | None | N | 0.242 | 0.062 | None | gnomAD-2.1.1 | 7.15E-06 | None | None | None | None | I | None | 4.13E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs552074847 |
0.084 | None | N | 0.242 | 0.062 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| V/I | rs552074847 |
0.084 | None | N | 0.242 | 0.062 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| V/I | rs552074847 |
0.084 | None | N | 0.242 | 0.062 | None | gnomAD-4.0.0 | 3.0448E-06 | None | None | None | None | I | None | 1.74386E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20498E-06 | 4.69969E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0899 | likely_benign | 0.0842 | benign | -0.396 | Destabilizing | None | N | 0.255 | neutral | N | 0.408163811 | None | None | I |
| V/C | 0.5113 | ambiguous | 0.4935 | ambiguous | -0.753 | Destabilizing | 0.824 | D | 0.36 | neutral | None | None | None | None | I |
| V/D | 0.1863 | likely_benign | 0.1757 | benign | -0.246 | Destabilizing | 0.001 | N | 0.379 | neutral | N | 0.421034321 | None | None | I |
| V/E | 0.1732 | likely_benign | 0.1701 | benign | -0.358 | Destabilizing | 0.081 | N | 0.415 | neutral | None | None | None | None | I |
| V/F | 0.1295 | likely_benign | 0.1176 | benign | -0.654 | Destabilizing | 0.317 | N | 0.355 | neutral | N | 0.470599136 | None | None | I |
| V/G | 0.1172 | likely_benign | 0.1138 | benign | -0.495 | Destabilizing | 0.062 | N | 0.441 | neutral | N | 0.432214106 | None | None | I |
| V/H | 0.3332 | likely_benign | 0.3041 | benign | -0.006 | Destabilizing | 0.935 | D | 0.411 | neutral | None | None | None | None | I |
| V/I | 0.0711 | likely_benign | 0.0672 | benign | -0.284 | Destabilizing | None | N | 0.242 | neutral | N | 0.428309797 | None | None | I |
| V/K | 0.2052 | likely_benign | 0.1941 | benign | -0.409 | Destabilizing | 0.38 | N | 0.401 | neutral | None | None | None | None | I |
| V/L | 0.1245 | likely_benign | 0.1142 | benign | -0.284 | Destabilizing | 0.009 | N | 0.451 | neutral | N | 0.461363577 | None | None | I |
| V/M | 0.1006 | likely_benign | 0.0978 | benign | -0.451 | Destabilizing | 0.38 | N | 0.366 | neutral | None | None | None | None | I |
| V/N | 0.1296 | likely_benign | 0.1128 | benign | -0.226 | Destabilizing | 0.235 | N | 0.431 | neutral | None | None | None | None | I |
| V/P | 0.3499 | ambiguous | 0.3276 | benign | -0.29 | Destabilizing | 0.555 | D | 0.415 | neutral | None | None | None | None | I |
| V/Q | 0.2035 | likely_benign | 0.1854 | benign | -0.44 | Destabilizing | 0.38 | N | 0.396 | neutral | None | None | None | None | I |
| V/R | 0.185 | likely_benign | 0.1702 | benign | 0.093 | Stabilizing | 0.555 | D | 0.418 | neutral | None | None | None | None | I |
| V/S | 0.0988 | likely_benign | 0.0891 | benign | -0.578 | Destabilizing | 0.081 | N | 0.413 | neutral | None | None | None | None | I |
| V/T | 0.0927 | likely_benign | 0.0843 | benign | -0.59 | Destabilizing | 0.002 | N | 0.319 | neutral | None | None | None | None | I |
| V/W | 0.5717 | likely_pathogenic | 0.5487 | ambiguous | -0.718 | Destabilizing | 0.935 | D | 0.565 | neutral | None | None | None | None | I |
| V/Y | 0.3554 | ambiguous | 0.3285 | benign | -0.437 | Destabilizing | 0.555 | D | 0.34 | 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.