Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26800 | 80623;80624;80625 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| N2AB | 25159 | 75700;75701;75702 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| N2A | 24232 | 72919;72920;72921 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| N2B | 17735 | 53428;53429;53430 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| Novex-1 | 17860 | 53803;53804;53805 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| Novex-2 | 17927 | 54004;54005;54006 | chr2:178565734;178565733;178565732 | chr2:179430461;179430460;179430459 |
| 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/K | None | None | 0.025 | N | 0.392 | 0.239 | 0.40218521252 | gnomAD-4.0.0 | 6.84288E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99572E-07 | 0 | 0 |
| M/L | None | None | None | N | 0.112 | 0.133 | 0.319686207203 | gnomAD-4.0.0 | 6.8429E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9958E-07 | 0 | 0 |
| M/T | rs761384994  |
-0.962 | None | N | 0.24 | 0.228 | 0.519783508757 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| M/T | rs761384994 |
-0.962 | None | N | 0.24 | 0.228 | 0.519783508757 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs761384994 |
-0.962 | None | N | 0.24 | 0.228 | 0.519783508757 | gnomAD-4.0.0 | 2.54113E-05 | None | None | None | None | N | None | 0 | 1.66761E-05 | None | 0 | 0 | None | 0 | 0 | 3.22134E-05 | 1.09789E-05 | 1.60169E-05 |
| M/V | None | None | None | N | 0.125 | 0.223 | 0.238705975628 | gnomAD-4.0.0 | 3.42145E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.4979E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1521 | likely_benign | 0.1562 | benign | -1.697 | Destabilizing | 0.006 | N | 0.264 | neutral | None | None | None | None | N |
| M/C | 0.4475 | ambiguous | 0.5306 | ambiguous | -1.466 | Destabilizing | None | N | 0.243 | neutral | None | None | None | None | N |
| M/D | 0.6112 | likely_pathogenic | 0.6216 | pathogenic | -0.77 | Destabilizing | 0.064 | N | 0.393 | neutral | None | None | None | None | N |
| M/E | 0.2775 | likely_benign | 0.2871 | benign | -0.708 | Destabilizing | 0.064 | N | 0.398 | neutral | None | None | None | None | N |
| M/F | 0.2272 | likely_benign | 0.2644 | benign | -0.687 | Destabilizing | 0.076 | N | 0.326 | neutral | None | None | None | None | N |
| M/G | 0.3218 | likely_benign | 0.3439 | ambiguous | -2.041 | Highly Destabilizing | 0.015 | N | 0.401 | neutral | None | None | None | None | N |
| M/H | 0.2568 | likely_benign | 0.2996 | benign | -1.265 | Destabilizing | 0.54 | D | 0.53 | neutral | None | None | None | None | N |
| M/I | 0.1696 | likely_benign | 0.1824 | benign | -0.793 | Destabilizing | 0.011 | N | 0.279 | neutral | N | 0.446253344 | None | None | N |
| M/K | 0.1219 | likely_benign | 0.1351 | benign | -0.543 | Destabilizing | 0.025 | N | 0.392 | neutral | N | 0.385164813 | None | None | N |
| M/L | 0.0959 | likely_benign | 0.1 | benign | -0.793 | Destabilizing | None | N | 0.112 | neutral | N | 0.409831184 | None | None | N |
| M/N | 0.225 | likely_benign | 0.2475 | benign | -0.504 | Destabilizing | 0.033 | N | 0.402 | neutral | None | None | None | None | N |
| M/P | 0.9573 | likely_pathogenic | 0.9465 | pathogenic | -1.067 | Destabilizing | 0.121 | N | 0.475 | neutral | None | None | None | None | N |
| M/Q | 0.1179 | likely_benign | 0.1373 | benign | -0.536 | Destabilizing | 0.142 | N | 0.326 | neutral | None | None | None | None | N |
| M/R | 0.1347 | likely_benign | 0.1462 | benign | -0.222 | Destabilizing | 0.049 | N | 0.44 | neutral | N | 0.381239073 | None | None | N |
| M/S | 0.1196 | likely_benign | 0.1291 | benign | -1.13 | Destabilizing | None | N | 0.209 | neutral | None | None | None | None | N |
| M/T | 0.0749 | likely_benign | 0.0795 | benign | -0.951 | Destabilizing | None | N | 0.24 | neutral | N | 0.355129908 | None | None | N |
| M/V | 0.0762 | likely_benign | 0.0821 | benign | -1.067 | Destabilizing | None | N | 0.125 | neutral | N | 0.402713211 | None | None | N |
| M/W | 0.5549 | ambiguous | 0.6051 | pathogenic | -0.708 | Destabilizing | 0.781 | D | 0.486 | neutral | None | None | None | None | N |
| M/Y | 0.3998 | ambiguous | 0.4422 | ambiguous | -0.672 | Destabilizing | 0.251 | N | 0.497 | neutral | None | None | None | None | N |
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.