Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31817 | 95674;95675;95676 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| N2AB | 30176 | 90751;90752;90753 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| N2A | 29249 | 87970;87971;87972 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| N2B | 22752 | 68479;68480;68481 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| Novex-1 | 22877 | 68854;68855;68856 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| Novex-2 | 22944 | 69055;69056;69057 | chr2:178545661;178545660;178545659 | chr2:179410388;179410387;179410386 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs758207460  |
-0.456 | 0.09 | N | 0.332 | 0.126 | 0.356281029322 | gnomAD-2.1.1 | 8.44E-05 | None | None | None | None | I | None | 0 | 4.92868E-04 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 1.65948E-04 |
| V/A | rs758207460 |
-0.456 | 0.09 | N | 0.332 | 0.126 | 0.356281029322 | gnomAD-3.1.2 | 1.7748E-04 | None | None | None | None | I | None | 0 | 1.76841E-03 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs758207460 |
-0.456 | 0.09 | N | 0.332 | 0.126 | 0.356281029322 | gnomAD-4.0.0 | 3.78062E-05 | None | None | None | None | I | None | 0 | 8.50198E-04 | None | 0 | 0 | None | 0 | 0 | 3.39091E-06 | 6.58848E-05 | 0 |
| V/L | rs1322909513 |
None | 0.015 | N | 0.173 | 0.036 | 0.282575091529 | 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 |
| V/L | rs1322909513 |
None | 0.015 | N | 0.173 | 0.036 | 0.282575091529 | gnomAD-4.0.0 | 6.57047E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46968E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0807 | likely_benign | 0.0827 | benign | -0.82 | Destabilizing | 0.09 | N | 0.332 | neutral | N | 0.432785402 | None | None | I |
| V/C | 0.5917 | likely_pathogenic | 0.61 | pathogenic | -0.836 | Destabilizing | 0.981 | D | 0.341 | neutral | None | None | None | None | I |
| V/D | 0.3105 | likely_benign | 0.3229 | benign | -0.571 | Destabilizing | 0.627 | D | 0.404 | neutral | N | 0.469783565 | None | None | I |
| V/E | 0.2751 | likely_benign | 0.2863 | benign | -0.658 | Destabilizing | 0.388 | N | 0.399 | neutral | None | None | None | None | I |
| V/F | 0.1403 | likely_benign | 0.1449 | benign | -0.792 | Destabilizing | 0.627 | D | 0.393 | neutral | N | 0.487601321 | None | None | I |
| V/G | 0.1682 | likely_benign | 0.1623 | benign | -1.003 | Destabilizing | 0.324 | N | 0.408 | neutral | N | 0.505840365 | None | None | I |
| V/H | 0.4836 | ambiguous | 0.4987 | ambiguous | -0.416 | Destabilizing | 0.981 | D | 0.33 | neutral | None | None | None | None | I |
| V/I | 0.0672 | likely_benign | 0.0691 | benign | -0.47 | Destabilizing | 0.001 | N | 0.125 | neutral | N | 0.45237124 | None | None | I |
| V/K | 0.3554 | ambiguous | 0.3717 | ambiguous | -0.791 | Destabilizing | 0.388 | N | 0.405 | neutral | None | None | None | None | I |
| V/L | 0.1611 | likely_benign | 0.1758 | benign | -0.47 | Destabilizing | 0.015 | N | 0.173 | neutral | N | 0.426955507 | None | None | I |
| V/M | 0.1065 | likely_benign | 0.1097 | benign | -0.5 | Destabilizing | 0.019 | N | 0.171 | neutral | None | None | None | None | I |
| V/N | 0.2107 | likely_benign | 0.2243 | benign | -0.583 | Destabilizing | 0.69 | D | 0.386 | neutral | None | None | None | None | I |
| V/P | 0.6584 | likely_pathogenic | 0.647 | pathogenic | -0.551 | Destabilizing | 0.818 | D | 0.367 | neutral | None | None | None | None | I |
| V/Q | 0.3172 | likely_benign | 0.3301 | benign | -0.825 | Destabilizing | 0.69 | D | 0.379 | neutral | None | None | None | None | I |
| V/R | 0.3222 | likely_benign | 0.3456 | ambiguous | -0.192 | Destabilizing | 0.69 | D | 0.397 | neutral | None | None | None | None | I |
| V/S | 0.1238 | likely_benign | 0.1276 | benign | -0.991 | Destabilizing | 0.024 | N | 0.207 | neutral | None | None | None | None | I |
| V/T | 0.0823 | likely_benign | 0.0863 | benign | -0.976 | Destabilizing | 0.004 | N | 0.075 | neutral | None | None | None | None | I |
| V/W | 0.695 | likely_pathogenic | 0.7081 | pathogenic | -0.858 | Destabilizing | 0.981 | D | 0.383 | neutral | None | None | None | None | I |
| V/Y | 0.4378 | ambiguous | 0.4672 | ambiguous | -0.593 | Destabilizing | 0.818 | D | 0.368 | 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.