Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18610 | 56053;56054;56055 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| N2AB | 16969 | 51130;51131;51132 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| N2A | 16042 | 48349;48350;48351 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| N2B | 9545 | 28858;28859;28860 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| Novex-1 | 9670 | 29233;29234;29235 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| Novex-2 | 9737 | 29434;29435;29436 | chr2:178601076;178601075;178601074 | chr2:179465803;179465802;179465801 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | rs1053494929  |
0.079 | 1.0 | N | 0.734 | 0.474 | 0.352048277211 | gnomAD-2.1.1 | 4.08E-06 | None | None | None | None | I | None | 6.5E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/S | rs1053494929 |
0.079 | 1.0 | N | 0.734 | 0.474 | 0.352048277211 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/S | rs1053494929 |
0.079 | 1.0 | N | 0.734 | 0.474 | 0.352048277211 | gnomAD-4.0.0 | 1.86341E-06 | None | None | None | None | I | None | 4.01768E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1037 | likely_benign | 0.0973 | benign | -0.297 | Destabilizing | 1.0 | D | 0.649 | neutral | N | 0.468890477 | None | None | I |
| P/C | 0.7223 | likely_pathogenic | 0.6844 | pathogenic | -0.468 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| P/D | 0.6528 | likely_pathogenic | 0.6353 | pathogenic | -0.188 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| P/E | 0.3942 | ambiguous | 0.3837 | ambiguous | -0.323 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/F | 0.701 | likely_pathogenic | 0.6648 | pathogenic | -0.747 | Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| P/G | 0.5106 | ambiguous | 0.5098 | ambiguous | -0.39 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| P/H | 0.3233 | likely_benign | 0.3061 | benign | -0.1 | Destabilizing | 1.0 | D | 0.609 | neutral | N | 0.495503882 | None | None | I |
| P/I | 0.4083 | ambiguous | 0.3817 | ambiguous | -0.215 | Destabilizing | 1.0 | D | 0.651 | neutral | None | None | None | None | I |
| P/K | 0.3466 | ambiguous | 0.3523 | ambiguous | -0.142 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| P/L | 0.181 | likely_benign | 0.1593 | benign | -0.215 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.504658141 | None | None | I |
| P/M | 0.4234 | ambiguous | 0.4084 | ambiguous | -0.126 | Destabilizing | 1.0 | D | 0.612 | neutral | None | None | None | None | I |
| P/N | 0.55 | ambiguous | 0.5385 | ambiguous | 0.116 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| P/Q | 0.2298 | likely_benign | 0.2194 | benign | -0.17 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| P/R | 0.2312 | likely_benign | 0.2179 | benign | 0.337 | Stabilizing | 1.0 | D | 0.671 | neutral | N | 0.484147576 | None | None | I |
| P/S | 0.2233 | likely_benign | 0.2094 | benign | -0.216 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | N | 0.483703049 | None | None | I |
| P/T | 0.1747 | likely_benign | 0.1696 | benign | -0.256 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.490210736 | None | None | I |
| P/V | 0.2634 | likely_benign | 0.245 | benign | -0.209 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| P/W | 0.8382 | likely_pathogenic | 0.8176 | pathogenic | -0.823 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | I |
| P/Y | 0.6807 | likely_pathogenic | 0.6542 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.598 | 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.