Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1565 | 4918;4919;4920 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| N2AB | 1565 | 4918;4919;4920 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| N2A | 1565 | 4918;4919;4920 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| N2B | 1519 | 4780;4781;4782 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| Novex-1 | 1519 | 4780;4781;4782 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| Novex-2 | 1519 | 4780;4781;4782 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
| Novex-3 | 1565 | 4918;4919;4920 | chr2:178777270;178777269;178777268 | chr2:179641997;179641996;179641995 |
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/A | rs1441856975  |
-1.113 | 0.052 | N | 0.327 | 0.315 | 0.540925512045 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/A | rs1441856975 |
-1.113 | 0.052 | N | 0.327 | 0.315 | 0.540925512045 | gnomAD-4.0.0 | 1.36825E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31868E-05 | 0 |
| V/D | rs1441856975 |
None | 0.484 | D | 0.461 | 0.556 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/D | rs1441856975 |
None | 0.484 | D | 0.461 | 0.556 | None | gnomAD-4.0.0 | 4.33723E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93229E-06 | 0 | 0 |
| V/I | rs762529971 |
-0.336 | None | N | 0.082 | 0.146 | 0.202949470691 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 1.77E-05 | 0 |
| V/I | rs762529971 |
-0.336 | None | N | 0.082 | 0.146 | 0.202949470691 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs762529971 |
-0.336 | None | N | 0.082 | 0.146 | 0.202949470691 | gnomAD-4.0.0 | 2.60237E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.47464E-05 | 1.09784E-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 | 0.2186 | likely_benign | 0.1896 | benign | -1.377 | Destabilizing | 0.052 | N | 0.327 | neutral | N | 0.521182998 | None | None | N |
| V/C | 0.6731 | likely_pathogenic | 0.5632 | ambiguous | -0.928 | Destabilizing | 0.935 | D | 0.323 | neutral | None | None | None | None | N |
| V/D | 0.5479 | ambiguous | 0.492 | ambiguous | -1.436 | Destabilizing | 0.484 | N | 0.461 | neutral | D | 0.685858454 | None | None | N |
| V/E | 0.3431 | ambiguous | 0.3026 | benign | -1.49 | Destabilizing | 0.555 | D | 0.408 | neutral | None | None | None | None | N |
| V/F | 0.1744 | likely_benign | 0.1589 | benign | -1.301 | Destabilizing | 0.188 | N | 0.362 | neutral | D | 0.622424101 | None | None | N |
| V/G | 0.363 | ambiguous | 0.3172 | benign | -1.64 | Destabilizing | 0.484 | N | 0.452 | neutral | D | 0.605777636 | None | None | N |
| V/H | 0.5107 | ambiguous | 0.4073 | ambiguous | -1.195 | Destabilizing | 0.935 | D | 0.423 | neutral | None | None | None | None | N |
| V/I | 0.0671 | likely_benign | 0.0628 | benign | -0.776 | Destabilizing | None | N | 0.082 | neutral | N | 0.503520137 | None | None | N |
| V/K | 0.3277 | likely_benign | 0.2713 | benign | -1.23 | Destabilizing | 0.38 | N | 0.419 | neutral | None | None | None | None | N |
| V/L | 0.0988 | likely_benign | 0.0854 | benign | -0.776 | Destabilizing | None | N | 0.071 | neutral | N | 0.512787391 | None | None | N |
| V/M | 0.0982 | likely_benign | 0.0883 | benign | -0.512 | Destabilizing | 0.007 | N | 0.233 | neutral | None | None | None | None | N |
| V/N | 0.3524 | ambiguous | 0.2816 | benign | -0.933 | Destabilizing | 0.555 | D | 0.45 | neutral | None | None | None | None | N |
| V/P | 0.9547 | likely_pathogenic | 0.9386 | pathogenic | -0.942 | Destabilizing | 0.791 | D | 0.429 | neutral | None | None | None | None | N |
| V/Q | 0.2808 | likely_benign | 0.2205 | benign | -1.183 | Destabilizing | 0.555 | D | 0.417 | neutral | None | None | None | None | N |
| V/R | 0.2863 | likely_benign | 0.2404 | benign | -0.591 | Destabilizing | 0.555 | D | 0.456 | neutral | None | None | None | None | N |
| V/S | 0.2942 | likely_benign | 0.2505 | benign | -1.345 | Destabilizing | 0.262 | N | 0.407 | neutral | None | None | None | None | N |
| V/T | 0.1877 | likely_benign | 0.1622 | benign | -1.293 | Destabilizing | 0.149 | N | 0.297 | neutral | None | None | None | None | N |
| V/W | 0.6981 | likely_pathogenic | 0.6076 | pathogenic | -1.43 | Destabilizing | 0.935 | D | 0.487 | neutral | None | None | None | None | N |
| V/Y | 0.5043 | ambiguous | 0.432 | ambiguous | -1.167 | Destabilizing | 0.555 | D | 0.359 | 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.