Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30317 | 91174;91175;91176 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| N2AB | 28676 | 86251;86252;86253 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| N2A | 27749 | 83470;83471;83472 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| N2B | 21252 | 63979;63980;63981 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| Novex-1 | 21377 | 64354;64355;64356 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| Novex-2 | 21444 | 64555;64556;64557 | chr2:178551951;178551950;178551949 | chr2:179416678;179416677;179416676 |
| 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 | rs759474127  |
-1.526 | 0.025 | N | 0.58 | 0.221 | None | gnomAD-2.1.1 | 3.57E-05 | None | None | None | None | N | None | 2.47872E-04 | 1.1318E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs759474127 |
-1.526 | 0.025 | N | 0.58 | 0.221 | None | gnomAD-3.1.2 | 8.54E-05 | None | None | None | None | N | None | 3.1354E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs759474127 |
-1.526 | 0.025 | N | 0.58 | 0.221 | None | gnomAD-4.0.0 | 2.04631E-05 | None | None | None | None | N | None | 2.93623E-04 | 8.33695E-05 | None | 0 | 0 | None | 0 | 0 | 2.54478E-06 | 0 | 4.806E-05 |
| V/E | rs759474127 |
-2.365 | 0.001 | D | 0.492 | 0.27 | 0.755777071576 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.3089E-04 | None | 0 | 0 | 0 |
| V/E | rs759474127 |
-2.365 | 0.001 | D | 0.492 | 0.27 | 0.755777071576 | gnomAD-4.0.0 | 8.90109E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.04384E-04 | 6.6302E-05 |
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 | 0.1332 | likely_benign | 0.1642 | benign | -0.941 | Destabilizing | 0.025 | N | 0.58 | neutral | N | 0.488273223 | None | None | N |
| V/C | 0.5826 | likely_pathogenic | 0.6716 | pathogenic | -0.846 | Destabilizing | 0.869 | D | 0.627 | neutral | None | None | None | None | N |
| V/D | 0.4097 | ambiguous | 0.5356 | ambiguous | -0.563 | Destabilizing | 0.125 | N | 0.768 | deleterious | None | None | None | None | N |
| V/E | 0.2558 | likely_benign | 0.3259 | benign | -0.605 | Destabilizing | 0.001 | N | 0.492 | neutral | D | 0.529227018 | None | None | N |
| V/F | 0.1468 | likely_benign | 0.1965 | benign | -0.742 | Destabilizing | 0.125 | N | 0.727 | deleterious | None | None | None | None | N |
| V/G | 0.2548 | likely_benign | 0.3387 | benign | -1.189 | Destabilizing | 0.303 | N | 0.759 | deleterious | N | 0.48954067 | None | None | N |
| V/H | 0.4086 | ambiguous | 0.497 | ambiguous | -0.609 | Destabilizing | 0.869 | D | 0.744 | deleterious | None | None | None | None | N |
| V/I | 0.0677 | likely_benign | 0.0698 | benign | -0.397 | Destabilizing | None | N | 0.121 | neutral | None | None | None | None | N |
| V/K | 0.2315 | likely_benign | 0.278 | benign | -0.862 | Destabilizing | 0.075 | N | 0.655 | prob.neutral | None | None | None | None | N |
| V/L | 0.1142 | likely_benign | 0.1422 | benign | -0.397 | Destabilizing | None | N | 0.173 | neutral | N | 0.499346828 | None | None | N |
| V/M | 0.102 | likely_benign | 0.117 | benign | -0.453 | Destabilizing | 0.097 | N | 0.675 | prob.neutral | D | 0.529920451 | None | None | N |
| V/N | 0.2468 | likely_benign | 0.3216 | benign | -0.665 | Destabilizing | 0.366 | N | 0.796 | deleterious | None | None | None | None | N |
| V/P | 0.4612 | ambiguous | 0.5411 | ambiguous | -0.542 | Destabilizing | 0.637 | D | 0.701 | prob.delet. | None | None | None | None | N |
| V/Q | 0.2347 | likely_benign | 0.2888 | benign | -0.839 | Destabilizing | 0.221 | N | 0.707 | prob.delet. | None | None | None | None | N |
| V/R | 0.2127 | likely_benign | 0.2636 | benign | -0.332 | Destabilizing | 0.221 | N | 0.792 | deleterious | None | None | None | None | N |
| V/S | 0.1865 | likely_benign | 0.2427 | benign | -1.146 | Destabilizing | 0.075 | N | 0.638 | neutral | None | None | None | None | N |
| V/T | 0.0992 | likely_benign | 0.1135 | benign | -1.074 | Destabilizing | 0.075 | N | 0.632 | neutral | None | None | None | None | N |
| V/W | 0.6701 | likely_pathogenic | 0.7863 | pathogenic | -0.857 | Destabilizing | 0.869 | D | 0.771 | deleterious | None | None | None | None | N |
| V/Y | 0.4162 | ambiguous | 0.5154 | ambiguous | -0.575 | Destabilizing | 0.366 | N | 0.721 | deleterious | 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.