Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28212 | 84859;84860;84861 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| N2AB | 26571 | 79936;79937;79938 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| N2A | 25644 | 77155;77156;77157 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| N2B | 19147 | 57664;57665;57666 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| Novex-1 | 19272 | 58039;58040;58041 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| Novex-2 | 19339 | 58240;58241;58242 | chr2:178561498;178561497;178561496 | chr2:179426225;179426224;179426223 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs527851457  |
0.165 | 0.97 | D | 0.636 | 0.406 | 0.530803083455 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | I | None | 0 | 1.45003E-04 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/I | rs527851457 |
0.165 | 0.97 | D | 0.636 | 0.406 | 0.530803083455 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 1.31027E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs527851457 |
0.165 | 0.97 | D | 0.636 | 0.406 | 0.530803083455 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/I | rs527851457 |
0.165 | 0.97 | D | 0.636 | 0.406 | 0.530803083455 | gnomAD-4.0.0 | 1.0249E-05 | None | None | None | None | I | None | 0 | 1.01667E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 2.68068E-05 | 0 |
| T/P | None | None | 0.99 | N | 0.637 | 0.467 | 0.510642626009 | gnomAD-4.0.0 | 1.59157E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85871E-06 | 0 | 0 |
| T/S | None | None | 0.822 | N | 0.49 | 0.327 | 0.317378411342 | gnomAD-4.0.0 | 1.59156E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85873E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1366 | likely_benign | 0.1384 | benign | -0.827 | Destabilizing | 0.822 | D | 0.46 | neutral | N | 0.489210004 | None | None | I |
| T/C | 0.3112 | likely_benign | 0.3344 | benign | -0.462 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | I |
| T/D | 0.561 | ambiguous | 0.5568 | ambiguous | -0.294 | Destabilizing | 0.754 | D | 0.545 | neutral | None | None | None | None | I |
| T/E | 0.4515 | ambiguous | 0.4409 | ambiguous | -0.166 | Destabilizing | 0.86 | D | 0.543 | neutral | None | None | None | None | I |
| T/F | 0.4725 | ambiguous | 0.4983 | ambiguous | -0.713 | Destabilizing | 0.993 | D | 0.688 | prob.neutral | None | None | None | None | I |
| T/G | 0.3078 | likely_benign | 0.3169 | benign | -1.187 | Destabilizing | 0.86 | D | 0.569 | neutral | None | None | None | None | I |
| T/H | 0.3275 | likely_benign | 0.3318 | benign | -1.287 | Destabilizing | 0.978 | D | 0.691 | prob.neutral | None | None | None | None | I |
| T/I | 0.3566 | ambiguous | 0.3661 | ambiguous | 0.079 | Stabilizing | 0.97 | D | 0.636 | neutral | D | 0.52623189 | None | None | I |
| T/K | 0.2003 | likely_benign | 0.2044 | benign | -0.309 | Destabilizing | 0.754 | D | 0.497 | neutral | None | None | None | None | I |
| T/L | 0.1056 | likely_benign | 0.1147 | benign | 0.079 | Stabilizing | 0.86 | D | 0.537 | neutral | None | None | None | None | I |
| T/M | 0.113 | likely_benign | 0.1178 | benign | 0.023 | Stabilizing | 0.998 | D | 0.641 | neutral | None | None | None | None | I |
| T/N | 0.1133 | likely_benign | 0.1146 | benign | -0.71 | Destabilizing | 0.058 | N | 0.254 | neutral | N | 0.476856649 | None | None | I |
| T/P | 0.2045 | likely_benign | 0.1867 | benign | -0.19 | Destabilizing | 0.99 | D | 0.637 | neutral | N | 0.491237921 | None | None | I |
| T/Q | 0.2409 | likely_benign | 0.2346 | benign | -0.585 | Destabilizing | 0.956 | D | 0.637 | neutral | None | None | None | None | I |
| T/R | 0.1621 | likely_benign | 0.1621 | benign | -0.372 | Destabilizing | 0.043 | N | 0.336 | neutral | None | None | None | None | I |
| T/S | 0.1368 | likely_benign | 0.1334 | benign | -1.026 | Destabilizing | 0.822 | D | 0.49 | neutral | N | 0.499605258 | None | None | I |
| T/V | 0.2348 | likely_benign | 0.2396 | benign | -0.19 | Destabilizing | 0.926 | D | 0.471 | neutral | None | None | None | None | I |
| T/W | 0.8211 | likely_pathogenic | 0.8278 | pathogenic | -0.784 | Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | I |
| T/Y | 0.4448 | ambiguous | 0.4663 | ambiguous | -0.425 | Destabilizing | 0.993 | D | 0.689 | prob.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.