Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17348 | 52267;52268;52269 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| N2AB | 15707 | 47344;47345;47346 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| N2A | 14780 | 44563;44564;44565 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| N2B | 8283 | 25072;25073;25074 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| Novex-1 | 8408 | 25447;25448;25449 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| Novex-2 | 8475 | 25648;25649;25650 | chr2:178609268;178609267;178609266 | chr2:179473995;179473994;179473993 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs758852311  |
-0.822 | 0.015 | N | 0.411 | 0.107 | 0.389750110748 | gnomAD-2.1.1 | 4.92E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 5.13E-05 | None | 0 | 0 | 0 |
| M/I | rs758852311 |
-0.822 | 0.015 | N | 0.411 | 0.107 | 0.389750110748 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 4.14422E-04 | 0 |
| M/I | rs758852311 |
-0.822 | 0.015 | N | 0.411 | 0.107 | 0.389750110748 | gnomAD-4.0.0 | 7.05167E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.37914E-04 | 0 |
| M/T | rs992739626 |
-1.509 | None | N | 0.249 | 0.184 | 0.365703291355 | gnomAD-2.1.1 | 4.88E-06 | None | None | None | None | I | None | 0 | 3.6E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs992739626 |
-1.509 | None | N | 0.249 | 0.184 | 0.365703291355 | gnomAD-4.0.0 | 4.25587E-06 | None | None | None | None | I | None | 0 | 2.7027E-05 | None | 0 | 0 | None | 0 | 0 | 4.58874E-06 | 0 | 0 |
| M/V | rs780570190 |
-1.189 | None | N | 0.141 | 0.221 | None | gnomAD-2.1.1 | 1.89E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.38464E-04 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs780570190 |
-1.189 | None | N | 0.141 | 0.221 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.94553E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs780570190 |
-1.189 | None | N | 0.141 | 0.221 | None | gnomAD-4.0.0 | 1.78335E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.09481E-04 | None | 0 | 0 | 8.61741E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3071 | likely_benign | 0.2715 | benign | -2.376 | Highly Destabilizing | 0.025 | N | 0.352 | neutral | None | None | None | None | I |
| M/C | 0.5332 | ambiguous | 0.5404 | ambiguous | -2.163 | Highly Destabilizing | 0.667 | D | 0.575 | neutral | None | None | None | None | I |
| M/D | 0.8539 | likely_pathogenic | 0.8156 | pathogenic | -1.82 | Destabilizing | 0.22 | N | 0.503 | neutral | None | None | None | None | I |
| M/E | 0.4589 | ambiguous | 0.4091 | ambiguous | -1.602 | Destabilizing | 0.22 | N | 0.539 | neutral | None | None | None | None | I |
| M/F | 0.3319 | likely_benign | 0.3042 | benign | -0.793 | Destabilizing | 0.22 | N | 0.463 | neutral | None | None | None | None | I |
| M/G | 0.5838 | likely_pathogenic | 0.5406 | ambiguous | -2.857 | Highly Destabilizing | 0.22 | N | 0.521 | neutral | None | None | None | None | I |
| M/H | 0.4723 | ambiguous | 0.4551 | ambiguous | -2.316 | Highly Destabilizing | 0.859 | D | 0.595 | neutral | None | None | None | None | I |
| M/I | 0.2782 | likely_benign | 0.2204 | benign | -1.001 | Destabilizing | 0.015 | N | 0.411 | neutral | N | 0.432560823 | None | None | I |
| M/K | 0.3189 | likely_benign | 0.2961 | benign | -1.502 | Destabilizing | 0.175 | N | 0.578 | neutral | N | 0.422863904 | None | None | I |
| M/L | 0.1542 | likely_benign | 0.1429 | benign | -1.001 | Destabilizing | 0.008 | N | 0.327 | neutral | N | 0.470001703 | None | None | I |
| M/N | 0.4593 | ambiguous | 0.4177 | ambiguous | -1.784 | Destabilizing | 0.22 | N | 0.515 | neutral | None | None | None | None | I |
| M/P | 0.9929 | likely_pathogenic | 0.9894 | pathogenic | -1.441 | Destabilizing | 0.364 | N | 0.522 | neutral | None | None | None | None | I |
| M/Q | 0.2773 | likely_benign | 0.2679 | benign | -1.506 | Destabilizing | 0.364 | N | 0.469 | neutral | None | None | None | None | I |
| M/R | 0.3316 | likely_benign | 0.3142 | benign | -1.474 | Destabilizing | 0.175 | N | 0.543 | neutral | N | 0.433656901 | None | None | I |
| M/S | 0.2745 | likely_benign | 0.2489 | benign | -2.421 | Highly Destabilizing | 0.055 | N | 0.491 | neutral | None | None | None | None | I |
| M/T | 0.1219 | likely_benign | 0.107 | benign | -2.077 | Highly Destabilizing | None | N | 0.249 | neutral | N | 0.357809561 | None | None | I |
| M/V | 0.0984 | likely_benign | 0.0857 | benign | -1.441 | Destabilizing | None | N | 0.141 | neutral | N | 0.432387465 | None | None | I |
| M/W | 0.6192 | likely_pathogenic | 0.6174 | pathogenic | -1.063 | Destabilizing | 0.958 | D | 0.555 | neutral | None | None | None | None | I |
| M/Y | 0.5186 | ambiguous | 0.5103 | ambiguous | -1.082 | Destabilizing | 0.667 | D | 0.591 | 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.