Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24724 | 74395;74396;74397 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| N2AB | 23083 | 69472;69473;69474 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| N2A | 22156 | 66691;66692;66693 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| N2B | 15659 | 47200;47201;47202 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| Novex-1 | 15784 | 47575;47576;47577 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| Novex-2 | 15851 | 47776;47777;47778 | chr2:178571962;178571961;178571960 | chr2:179436689;179436688;179436687 |
| 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/A | None | None | 0.919 | N | 0.393 | 0.281 | 0.239901079897 | gnomAD-4.0.0 | 1.59237E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85953E-06 | 0 | 0 |
| T/I | rs528199512  |
-0.073 | 0.919 | N | 0.591 | 0.435 | 0.33340067248 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| T/I | rs528199512 |
-0.073 | 0.919 | N | 0.591 | 0.435 | 0.33340067248 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| T/I | rs528199512 |
-0.073 | 0.919 | N | 0.591 | 0.435 | 0.33340067248 | gnomAD-4.0.0 | 6.56849E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.41442E-05 | 0 | 0 | 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 | 0.1379 | likely_benign | 0.1393 | benign | -0.783 | Destabilizing | 0.919 | D | 0.393 | neutral | N | 0.511427038 | None | None | I |
| T/C | 0.5995 | likely_pathogenic | 0.6209 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.647 | neutral | None | None | None | None | I |
| T/D | 0.5531 | ambiguous | 0.5911 | pathogenic | 0.245 | Stabilizing | 0.998 | D | 0.719 | prob.delet. | None | None | None | None | I |
| T/E | 0.5263 | ambiguous | 0.5594 | ambiguous | 0.254 | Stabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | I |
| T/F | 0.5914 | likely_pathogenic | 0.5874 | pathogenic | -0.87 | Destabilizing | 0.991 | D | 0.724 | prob.delet. | None | None | None | None | I |
| T/G | 0.4452 | ambiguous | 0.4397 | ambiguous | -1.04 | Destabilizing | 0.995 | D | 0.64 | neutral | None | None | None | None | I |
| T/H | 0.365 | ambiguous | 0.3685 | ambiguous | -1.238 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| T/I | 0.3147 | likely_benign | 0.3223 | benign | -0.19 | Destabilizing | 0.919 | D | 0.591 | neutral | N | 0.478809572 | None | None | I |
| T/K | 0.4239 | ambiguous | 0.4389 | ambiguous | -0.539 | Destabilizing | 0.995 | D | 0.709 | prob.delet. | None | None | None | None | I |
| T/L | 0.2192 | likely_benign | 0.219 | benign | -0.19 | Destabilizing | 0.938 | D | 0.439 | neutral | None | None | None | None | I |
| T/M | 0.1597 | likely_benign | 0.1514 | benign | -0.039 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| T/N | 0.1472 | likely_benign | 0.1474 | benign | -0.475 | Destabilizing | 0.998 | D | 0.615 | neutral | N | 0.485469801 | None | None | I |
| T/P | 0.473 | ambiguous | 0.4991 | ambiguous | -0.355 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | N | 0.510386888 | None | None | I |
| T/Q | 0.3666 | ambiguous | 0.3613 | ambiguous | -0.569 | Destabilizing | 0.998 | D | 0.699 | prob.neutral | None | None | None | None | I |
| T/R | 0.3599 | ambiguous | 0.3694 | ambiguous | -0.376 | Destabilizing | 0.995 | D | 0.701 | prob.neutral | None | None | None | None | I |
| T/S | 0.1299 | likely_benign | 0.1288 | benign | -0.818 | Destabilizing | 0.979 | D | 0.405 | neutral | N | 0.478197112 | None | None | I |
| T/V | 0.2211 | likely_benign | 0.2273 | benign | -0.355 | Destabilizing | 0.086 | N | 0.289 | neutral | None | None | None | None | I |
| T/W | 0.8662 | likely_pathogenic | 0.8772 | pathogenic | -0.81 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| T/Y | 0.4753 | ambiguous | 0.4908 | ambiguous | -0.566 | Destabilizing | 0.995 | D | 0.728 | prob.delet. | 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.