Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18122 | 54589;54590;54591 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| N2AB | 16481 | 49666;49667;49668 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| N2A | 15554 | 46885;46886;46887 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| N2B | 9057 | 27394;27395;27396 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| Novex-1 | 9182 | 27769;27770;27771 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| Novex-2 | 9249 | 27970;27971;27972 | chr2:178604725;178604724;178604723 | chr2:179469452;179469451;179469450 |
| 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 | rs563319285  |
-0.249 | 0.122 | N | 0.16 | 0.08 | 0.231231049324 | gnomAD-2.1.1 | 3.64E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 2.97895E-04 | None | 0 | 0 | 0 |
| V/I | rs563319285 |
-0.249 | 0.122 | N | 0.16 | 0.08 | 0.231231049324 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| V/I | rs563319285 |
-0.249 | 0.122 | N | 0.16 | 0.08 | 0.231231049324 | 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 | rs563319285 |
-0.249 | 0.122 | N | 0.16 | 0.08 | 0.231231049324 | gnomAD-4.0.0 | 1.86266E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.0918E-04 | 3.20924E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1499 | likely_benign | 0.1631 | benign | -0.844 | Destabilizing | 0.91 | D | 0.487 | neutral | N | 0.421298971 | None | None | I |
| V/C | 0.7164 | likely_pathogenic | 0.7312 | pathogenic | -0.765 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | I |
| V/D | 0.4146 | ambiguous | 0.4966 | ambiguous | -0.304 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | I |
| V/E | 0.3003 | likely_benign | 0.3301 | benign | -0.339 | Destabilizing | 0.998 | D | 0.552 | neutral | N | 0.431534608 | None | None | I |
| V/F | 0.1904 | likely_benign | 0.2037 | benign | -0.639 | Destabilizing | 0.996 | D | 0.535 | neutral | None | None | None | None | I |
| V/G | 0.1812 | likely_benign | 0.2146 | benign | -1.088 | Destabilizing | 0.998 | D | 0.581 | neutral | N | 0.40205985 | None | None | I |
| V/H | 0.5524 | ambiguous | 0.6144 | pathogenic | -0.491 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | I |
| V/I | 0.0806 | likely_benign | 0.0775 | benign | -0.31 | Destabilizing | 0.122 | N | 0.16 | neutral | N | 0.40608159 | None | None | I |
| V/K | 0.2799 | likely_benign | 0.3172 | benign | -0.714 | Destabilizing | 0.999 | D | 0.558 | neutral | None | None | None | None | I |
| V/L | 0.1654 | likely_benign | 0.1783 | benign | -0.31 | Destabilizing | 0.689 | D | 0.319 | neutral | N | 0.476114891 | None | None | I |
| V/M | 0.1396 | likely_benign | 0.1298 | benign | -0.425 | Destabilizing | 0.996 | D | 0.489 | neutral | None | None | None | None | I |
| V/N | 0.2542 | likely_benign | 0.3364 | benign | -0.546 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | I |
| V/P | 0.3532 | ambiguous | 0.4337 | ambiguous | -0.452 | Destabilizing | 0.999 | D | 0.543 | neutral | None | None | None | None | I |
| V/Q | 0.2854 | likely_benign | 0.3079 | benign | -0.688 | Destabilizing | 0.999 | D | 0.563 | neutral | None | None | None | None | I |
| V/R | 0.279 | likely_benign | 0.3085 | benign | -0.241 | Destabilizing | 0.999 | D | 0.587 | neutral | None | None | None | None | I |
| V/S | 0.1753 | likely_benign | 0.2265 | benign | -1.043 | Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | I |
| V/T | 0.1476 | likely_benign | 0.156 | benign | -0.961 | Destabilizing | 0.985 | D | 0.461 | neutral | None | None | None | None | I |
| V/W | 0.7763 | likely_pathogenic | 0.776 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.629 | neutral | None | None | None | None | I |
| V/Y | 0.5443 | ambiguous | 0.5902 | pathogenic | -0.468 | Destabilizing | 0.999 | D | 0.521 | 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.