Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28366 | 85321;85322;85323 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| N2AB | 26725 | 80398;80399;80400 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| N2A | 25798 | 77617;77618;77619 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| N2B | 19301 | 58126;58127;58128 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| Novex-1 | 19426 | 58501;58502;58503 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| Novex-2 | 19493 | 58702;58703;58704 | chr2:178561036;178561035;178561034 | chr2:179425763;179425762;179425761 |
| 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 | rs1003730939  |
None | 0.09 | N | 0.341 | 0.077 | 0.273938319068 | gnomAD-4.0.0 | 1.59109E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85802E-06 | 0 | 0 |
| V/I | rs367800789 |
-0.345 | 0.008 | N | 0.21 | 0.044 | None | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 1.39276E-04 | 3.56E-05 | 0 |
| V/I | rs367800789 |
-0.345 | 0.008 | N | 0.21 | 0.044 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| V/I | rs367800789 |
-0.345 | 0.008 | N | 0.21 | 0.044 | None | gnomAD-4.0.0 | 3.65613E-05 | None | None | None | None | I | None | 1.33486E-05 | 0 | None | 0 | 0 | None | 1.71832E-04 | 0 | 3.13611E-05 | 9.88186E-05 | 1.60097E-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 | 0.1889 | likely_benign | 0.143 | benign | -0.686 | Destabilizing | 0.09 | N | 0.341 | neutral | N | 0.449146429 | None | None | I |
| V/C | 0.6793 | likely_pathogenic | 0.6036 | pathogenic | -0.682 | Destabilizing | 0.981 | D | 0.391 | neutral | None | None | None | None | I |
| V/D | 0.3768 | ambiguous | 0.2488 | benign | -0.328 | Destabilizing | 0.627 | D | 0.507 | neutral | N | 0.426381425 | None | None | I |
| V/E | 0.3253 | likely_benign | 0.246 | benign | -0.432 | Destabilizing | 0.818 | D | 0.469 | neutral | None | None | None | None | I |
| V/F | 0.2108 | likely_benign | 0.1595 | benign | -0.841 | Destabilizing | 0.81 | D | 0.395 | neutral | N | 0.493302638 | None | None | I |
| V/G | 0.2081 | likely_benign | 0.1609 | benign | -0.851 | Destabilizing | 0.001 | N | 0.356 | neutral | N | 0.447722277 | None | None | I |
| V/H | 0.5916 | likely_pathogenic | 0.4803 | ambiguous | -0.432 | Destabilizing | 0.981 | D | 0.501 | neutral | None | None | None | None | I |
| V/I | 0.0794 | likely_benign | 0.0809 | benign | -0.392 | Destabilizing | 0.008 | N | 0.21 | neutral | N | 0.511888398 | None | None | I |
| V/K | 0.362 | ambiguous | 0.2715 | benign | -0.545 | Destabilizing | 0.69 | D | 0.471 | neutral | None | None | None | None | I |
| V/L | 0.1911 | likely_benign | 0.1569 | benign | -0.392 | Destabilizing | 0.001 | N | 0.106 | neutral | N | 0.430734026 | None | None | I |
| V/M | 0.1318 | likely_benign | 0.1079 | benign | -0.352 | Destabilizing | 0.69 | D | 0.401 | neutral | None | None | None | None | I |
| V/N | 0.239 | likely_benign | 0.1605 | benign | -0.251 | Destabilizing | 0.69 | D | 0.516 | neutral | None | None | None | None | I |
| V/P | 0.6739 | likely_pathogenic | 0.5179 | ambiguous | -0.454 | Destabilizing | 0.932 | D | 0.491 | neutral | None | None | None | None | I |
| V/Q | 0.3599 | ambiguous | 0.2875 | benign | -0.501 | Destabilizing | 0.932 | D | 0.493 | neutral | None | None | None | None | I |
| V/R | 0.3348 | likely_benign | 0.2475 | benign | -0.024 | Destabilizing | 0.818 | D | 0.519 | neutral | None | None | None | None | I |
| V/S | 0.2144 | likely_benign | 0.1502 | benign | -0.666 | Destabilizing | 0.388 | N | 0.43 | neutral | None | None | None | None | I |
| V/T | 0.1454 | likely_benign | 0.1078 | benign | -0.664 | Destabilizing | 0.388 | N | 0.301 | neutral | None | None | None | None | I |
| V/W | 0.8304 | likely_pathogenic | 0.734 | pathogenic | -0.909 | Destabilizing | 0.981 | D | 0.552 | neutral | None | None | None | None | I |
| V/Y | 0.5141 | ambiguous | 0.4116 | ambiguous | -0.612 | Destabilizing | 0.818 | D | 0.41 | 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.