Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3424 | 10495;10496;10497 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| N2AB | 3424 | 10495;10496;10497 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| N2A | 3424 | 10495;10496;10497 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| N2B | 3378 | 10357;10358;10359 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| Novex-1 | 3378 | 10357;10358;10359 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| Novex-2 | 3378 | 10357;10358;10359 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
| Novex-3 | 3424 | 10495;10496;10497 | chr2:178759017;178759016;178759015 | chr2:179623744;179623743;179623742 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/K | rs370865998  |
0.326 | 0.514 | N | 0.345 | 0.3 | None | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.33E-05 | 1.38696E-04 |
| Q/K | rs370865998 |
0.326 | 0.514 | N | 0.345 | 0.3 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| Q/K | rs370865998 |
0.326 | 0.514 | N | 0.345 | 0.3 | None | gnomAD-4.0.0 | 3.03636E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.81382E-05 | 0 | 6.40246E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q/A | 0.2792 | likely_benign | 0.3119 | benign | -0.315 | Destabilizing | 0.737 | D | 0.388 | neutral | None | None | None | None | I |
| Q/C | 0.7252 | likely_pathogenic | 0.7228 | pathogenic | 0.106 | Stabilizing | 0.998 | D | 0.487 | neutral | None | None | None | None | I |
| Q/D | 0.4574 | ambiguous | 0.5376 | ambiguous | 0.089 | Stabilizing | 0.584 | D | 0.345 | neutral | None | None | None | None | I |
| Q/E | 0.0872 | likely_benign | 0.0886 | benign | 0.062 | Stabilizing | 0.028 | N | 0.172 | neutral | N | 0.409938236 | None | None | I |
| Q/F | 0.7314 | likely_pathogenic | 0.7606 | pathogenic | -0.5 | Destabilizing | 0.96 | D | 0.503 | neutral | None | None | None | None | I |
| Q/G | 0.4066 | ambiguous | 0.4511 | ambiguous | -0.502 | Destabilizing | 0.85 | D | 0.5 | neutral | None | None | None | None | I |
| Q/H | 0.2404 | likely_benign | 0.2762 | benign | -0.401 | Destabilizing | 0.991 | D | 0.405 | neutral | N | 0.51530934 | None | None | I |
| Q/I | 0.4345 | ambiguous | 0.4462 | ambiguous | 0.09 | Stabilizing | 0.773 | D | 0.554 | neutral | None | None | None | None | I |
| Q/K | 0.0959 | likely_benign | 0.1046 | benign | 0.084 | Stabilizing | 0.514 | D | 0.345 | neutral | N | 0.447505699 | None | None | I |
| Q/L | 0.1885 | likely_benign | 0.1933 | benign | 0.09 | Stabilizing | 0.514 | D | 0.495 | neutral | N | 0.514519773 | None | None | I |
| Q/M | 0.3847 | ambiguous | 0.3799 | ambiguous | 0.379 | Stabilizing | 0.38 | N | 0.232 | neutral | None | None | None | None | I |
| Q/N | 0.3362 | likely_benign | 0.3984 | ambiguous | -0.288 | Destabilizing | 0.932 | D | 0.341 | neutral | None | None | None | None | I |
| Q/P | 0.5592 | ambiguous | 0.6621 | pathogenic | -0.017 | Destabilizing | 0.969 | D | 0.515 | neutral | N | 0.514709059 | None | None | I |
| Q/R | 0.1144 | likely_benign | 0.1249 | benign | 0.226 | Stabilizing | 0.016 | N | 0.198 | neutral | N | 0.491818601 | None | None | I |
| Q/S | 0.2739 | likely_benign | 0.3251 | benign | -0.304 | Destabilizing | 0.584 | D | 0.356 | neutral | None | None | None | None | I |
| Q/T | 0.1994 | likely_benign | 0.2338 | benign | -0.171 | Destabilizing | 0.037 | N | 0.209 | neutral | None | None | None | None | I |
| Q/V | 0.2951 | likely_benign | 0.3022 | benign | -0.017 | Destabilizing | 0.584 | D | 0.523 | neutral | None | None | None | None | I |
| Q/W | 0.6363 | likely_pathogenic | 0.6448 | pathogenic | -0.437 | Destabilizing | 0.998 | D | 0.499 | neutral | None | None | None | None | I |
| Q/Y | 0.5253 | ambiguous | 0.5514 | ambiguous | -0.194 | Destabilizing | 0.993 | D | 0.475 | 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.