Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2771 | 8536;8537;8538 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| N2AB | 2771 | 8536;8537;8538 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| N2A | 2771 | 8536;8537;8538 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| N2B | 2725 | 8398;8399;8400 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| Novex-1 | 2725 | 8398;8399;8400 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| Novex-2 | 2725 | 8398;8399;8400 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
| Novex-3 | 2771 | 8536;8537;8538 | chr2:178770481;178770480;178770479 | chr2:179635208;179635207;179635206 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | rs576644663  |
-0.171 | 0.001 | N | 0.213 | 0.254 | 0.0920862733494 | gnomAD-2.1.1 | 1.06E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.50678E-04 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs576644663 |
-0.171 | 0.001 | N | 0.213 | 0.254 | 0.0920862733494 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.9253E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs576644663 |
-0.171 | 0.001 | N | 0.213 | 0.254 | 0.0920862733494 | gnomAD-4.0.0 | 1.85874E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.68509E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs780465670 |
-0.128 | None | N | 0.089 | 0.244 | None | gnomAD-2.1.1 | 1.42E-05 | None | None | None | None | I | None | 4.01E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.33E-05 | 0 |
| I/T | rs780465670 |
-0.128 | None | N | 0.089 | 0.244 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs780465670 |
-0.128 | None | N | 0.089 | 0.244 | None | gnomAD-4.0.0 | 5.20422E-05 | None | None | None | None | I | None | 6.67111E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.52526E-05 | 0 | 3.20072E-05 |
| I/V | rs1416391085 |
0.041 | None | N | 0.081 | 0.216 | 0.339793275041 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| I/V | rs1416391085 |
0.041 | None | N | 0.081 | 0.216 | 0.339793275041 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/V | rs1416391085 |
0.041 | None | N | 0.081 | 0.216 | 0.339793275041 | gnomAD-4.0.0 | 6.56935E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46972E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1155 | likely_benign | 0.1236 | benign | -0.355 | Destabilizing | None | N | 0.107 | neutral | None | None | None | None | I |
| I/C | 0.6359 | likely_pathogenic | 0.6371 | pathogenic | -0.491 | Destabilizing | 0.245 | N | 0.169 | neutral | None | None | None | None | I |
| I/D | 0.4905 | ambiguous | 0.5439 | ambiguous | -0.303 | Destabilizing | 0.044 | N | 0.287 | neutral | None | None | None | None | I |
| I/E | 0.4004 | ambiguous | 0.4329 | ambiguous | -0.414 | Destabilizing | 0.018 | N | 0.225 | neutral | None | None | None | None | I |
| I/F | 0.1636 | likely_benign | 0.1572 | benign | -0.588 | Destabilizing | 0.033 | N | 0.147 | neutral | N | 0.502841143 | None | None | I |
| I/G | 0.3616 | ambiguous | 0.3811 | ambiguous | -0.47 | Destabilizing | 0.018 | N | 0.223 | neutral | None | None | None | None | I |
| I/H | 0.4098 | ambiguous | 0.4367 | ambiguous | 0.067 | Stabilizing | 0.497 | N | 0.247 | neutral | None | None | None | None | I |
| I/K | 0.2437 | likely_benign | 0.2795 | benign | -0.225 | Destabilizing | 0.018 | N | 0.211 | neutral | None | None | None | None | I |
| I/L | 0.0899 | likely_benign | 0.0784 | benign | -0.186 | Destabilizing | None | N | 0.063 | neutral | N | 0.451195511 | None | None | I |
| I/M | 0.0785 | likely_benign | 0.0729 | benign | -0.349 | Destabilizing | 0.001 | N | 0.213 | neutral | N | 0.477494841 | None | None | I |
| I/N | 0.1726 | likely_benign | 0.2234 | benign | 0.034 | Stabilizing | 0.033 | N | 0.307 | neutral | D | 0.546892802 | None | None | I |
| I/P | 0.2901 | likely_benign | 0.2984 | benign | -0.212 | Destabilizing | None | N | 0.186 | neutral | None | None | None | None | I |
| I/Q | 0.2982 | likely_benign | 0.3154 | benign | -0.202 | Destabilizing | 0.044 | N | 0.311 | neutral | None | None | None | None | I |
| I/R | 0.2002 | likely_benign | 0.2374 | benign | 0.275 | Stabilizing | 0.044 | N | 0.321 | neutral | None | None | None | None | I |
| I/S | 0.1407 | likely_benign | 0.1786 | benign | -0.312 | Destabilizing | 0.001 | N | 0.123 | neutral | N | 0.477524371 | None | None | I |
| I/T | 0.0857 | likely_benign | 0.0954 | benign | -0.323 | Destabilizing | None | N | 0.089 | neutral | N | 0.429027236 | None | None | I |
| I/V | 0.0595 | likely_benign | 0.0571 | benign | -0.212 | Destabilizing | None | N | 0.081 | neutral | N | 0.420773132 | None | None | I |
| I/W | 0.7558 | likely_pathogenic | 0.7021 | pathogenic | -0.632 | Destabilizing | 0.788 | D | 0.259 | neutral | None | None | None | None | I |
| I/Y | 0.4732 | ambiguous | 0.5174 | ambiguous | -0.359 | Destabilizing | 0.085 | N | 0.263 | 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.