Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17102 | 51529;51530;51531 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| N2AB | 15461 | 46606;46607;46608 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| N2A | 14534 | 43825;43826;43827 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| N2B | 8037 | 24334;24335;24336 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| Novex-1 | 8162 | 24709;24710;24711 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| Novex-2 | 8229 | 24910;24911;24912 | chr2:178610222;178610221;178610220 | chr2:179474949;179474948;179474947 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | rs1184311554  |
0.496 | 0.026 | N | 0.212 | 0.12 | 0.201204373187 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| N/D | rs1184311554 |
0.496 | 0.026 | N | 0.212 | 0.12 | 0.201204373187 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/D | rs1184311554 |
0.496 | 0.026 | N | 0.212 | 0.12 | 0.201204373187 | gnomAD-4.0.0 | 3.84719E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18742E-06 | 0 | 0 |
| N/K | rs1290588810 |
0.385 | 0.103 | N | 0.299 | 0.092 | 0.0884992946249 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| N/K | rs1290588810 |
0.385 | 0.103 | N | 0.299 | 0.092 | 0.0884992946249 | gnomAD-4.0.0 | 2.73795E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59917E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.4074 | ambiguous | 0.4137 | ambiguous | -0.637 | Destabilizing | 0.919 | D | 0.472 | neutral | None | None | None | None | I |
| N/C | 0.5242 | ambiguous | 0.537 | ambiguous | 0.063 | Stabilizing | 0.999 | D | 0.629 | neutral | None | None | None | None | I |
| N/D | 0.2244 | likely_benign | 0.2497 | benign | -0.264 | Destabilizing | 0.026 | N | 0.212 | neutral | N | 0.459625286 | None | None | I |
| N/E | 0.4999 | ambiguous | 0.5247 | ambiguous | -0.169 | Destabilizing | 0.851 | D | 0.458 | neutral | None | None | None | None | I |
| N/F | 0.81 | likely_pathogenic | 0.82 | pathogenic | -0.44 | Destabilizing | 0.996 | D | 0.586 | neutral | None | None | None | None | I |
| N/G | 0.3906 | ambiguous | 0.397 | ambiguous | -0.963 | Destabilizing | 0.919 | D | 0.452 | neutral | None | None | None | None | I |
| N/H | 0.2369 | likely_benign | 0.2371 | benign | -0.739 | Destabilizing | 0.995 | D | 0.489 | neutral | N | 0.503666852 | None | None | I |
| N/I | 0.5077 | ambiguous | 0.5276 | ambiguous | 0.182 | Stabilizing | 0.984 | D | 0.585 | neutral | D | 0.522041969 | None | None | I |
| N/K | 0.4977 | ambiguous | 0.5035 | ambiguous | -0.269 | Destabilizing | 0.103 | N | 0.299 | neutral | N | 0.429227808 | None | None | I |
| N/L | 0.4566 | ambiguous | 0.4548 | ambiguous | 0.182 | Stabilizing | 0.988 | D | 0.545 | neutral | None | None | None | None | I |
| N/M | 0.4954 | ambiguous | 0.5084 | ambiguous | 0.36 | Stabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | I |
| N/P | 0.601 | likely_pathogenic | 0.5949 | pathogenic | -0.061 | Destabilizing | 0.988 | D | 0.558 | neutral | None | None | None | None | I |
| N/Q | 0.4518 | ambiguous | 0.4508 | ambiguous | -0.677 | Destabilizing | 0.976 | D | 0.47 | neutral | None | None | None | None | I |
| N/R | 0.5986 | likely_pathogenic | 0.5956 | pathogenic | -0.359 | Destabilizing | 0.952 | D | 0.454 | neutral | None | None | None | None | I |
| N/S | 0.1528 | likely_benign | 0.1532 | benign | -0.776 | Destabilizing | 0.896 | D | 0.477 | neutral | N | 0.467012618 | None | None | I |
| N/T | 0.2606 | likely_benign | 0.2624 | benign | -0.497 | Destabilizing | 0.946 | D | 0.465 | neutral | N | 0.452600526 | None | None | I |
| N/V | 0.4676 | ambiguous | 0.4798 | ambiguous | -0.061 | Destabilizing | 0.988 | D | 0.585 | neutral | None | None | None | None | I |
| N/W | 0.9013 | likely_pathogenic | 0.9111 | pathogenic | -0.312 | Destabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | I |
| N/Y | 0.3151 | likely_benign | 0.3339 | benign | -0.076 | Destabilizing | 0.995 | D | 0.563 | neutral | N | 0.485259985 | 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.