Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30764 | 92515;92516;92517 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| N2AB | 29123 | 87592;87593;87594 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| N2A | 28196 | 84811;84812;84813 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| N2B | 21699 | 65320;65321;65322 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| Novex-1 | 21824 | 65695;65696;65697 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| Novex-2 | 21891 | 65896;65897;65898 | chr2:178549336;178549335;178549334 | chr2:179414063;179414062;179414061 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs376537509  |
0.09 | 0.175 | N | 0.333 | 0.167 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| T/K | rs376537509 |
0.09 | 0.175 | N | 0.333 | 0.167 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/K | rs376537509 |
0.09 | 0.175 | N | 0.333 | 0.167 | None | gnomAD-4.0.0 | 1.92099E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62748E-05 | 0 | 0 |
| T/S | None | None | 0.081 | N | 0.283 | 0.091 | 0.151104730317 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.07 | likely_benign | 0.0698 | benign | -0.241 | Destabilizing | 0.019 | N | 0.305 | neutral | N | 0.46087608 | None | None | N |
| T/C | 0.3225 | likely_benign | 0.3452 | ambiguous | -0.339 | Destabilizing | 0.859 | D | 0.341 | neutral | None | None | None | None | N |
| T/D | 0.4622 | ambiguous | 0.4397 | ambiguous | 0.121 | Stabilizing | 0.364 | N | 0.345 | neutral | None | None | None | None | N |
| T/E | 0.3634 | ambiguous | 0.3458 | ambiguous | 0.032 | Stabilizing | 0.364 | N | 0.32 | neutral | None | None | None | None | N |
| T/F | 0.2031 | likely_benign | 0.2027 | benign | -0.883 | Destabilizing | 0.22 | N | 0.315 | neutral | None | None | None | None | N |
| T/G | 0.1593 | likely_benign | 0.1592 | benign | -0.311 | Destabilizing | 0.364 | N | 0.309 | neutral | None | None | None | None | N |
| T/H | 0.249 | likely_benign | 0.2458 | benign | -0.467 | Destabilizing | 0.859 | D | 0.319 | neutral | None | None | None | None | N |
| T/I | 0.1072 | likely_benign | 0.1105 | benign | -0.18 | Destabilizing | None | N | 0.197 | neutral | N | 0.43194004 | None | None | N |
| T/K | 0.2413 | likely_benign | 0.2326 | benign | -0.266 | Destabilizing | 0.175 | N | 0.333 | neutral | N | 0.471573076 | None | None | N |
| T/L | 0.0613 | likely_benign | 0.0597 | benign | -0.18 | Destabilizing | None | N | 0.173 | neutral | None | None | None | None | N |
| T/M | 0.0713 | likely_benign | 0.0686 | benign | -0.162 | Destabilizing | 0.002 | N | 0.201 | neutral | None | None | None | None | N |
| T/N | 0.1117 | likely_benign | 0.1078 | benign | -0.064 | Destabilizing | 0.364 | N | 0.303 | neutral | None | None | None | None | N |
| T/P | 0.094 | likely_benign | 0.0864 | benign | -0.176 | Destabilizing | 0.822 | D | 0.365 | neutral | N | 0.476152177 | None | None | N |
| T/Q | 0.2071 | likely_benign | 0.1996 | benign | -0.272 | Destabilizing | 0.497 | N | 0.357 | neutral | None | None | None | None | N |
| T/R | 0.1977 | likely_benign | 0.1978 | benign | 0.029 | Stabilizing | 0.175 | N | 0.345 | neutral | N | 0.475133456 | None | None | N |
| T/S | 0.0922 | likely_benign | 0.0907 | benign | -0.253 | Destabilizing | 0.081 | N | 0.283 | neutral | N | 0.451467163 | None | None | N |
| T/V | 0.0886 | likely_benign | 0.0895 | benign | -0.176 | Destabilizing | 0.025 | N | 0.289 | neutral | None | None | None | None | N |
| T/W | 0.5118 | ambiguous | 0.4926 | ambiguous | -0.947 | Destabilizing | 0.958 | D | 0.317 | neutral | None | None | None | None | N |
| T/Y | 0.2564 | likely_benign | 0.2491 | benign | -0.631 | Destabilizing | 0.667 | D | 0.337 | neutral | None | None | None | None | N |
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.