Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31833 | 95722;95723;95724 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| N2AB | 30192 | 90799;90800;90801 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| N2A | 29265 | 88018;88019;88020 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| N2B | 22768 | 68527;68528;68529 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| Novex-1 | 22893 | 68902;68903;68904 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| Novex-2 | 22960 | 69103;69104;69105 | chr2:178545613;178545612;178545611 | chr2:179410340;179410339;179410338 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/T | rs764271138  |
0.071 | 0.22 | N | 0.39 | 0.129 | 0.181679512989 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.55E-05 | 0 |
| S/T | rs764271138 |
0.071 | 0.22 | N | 0.39 | 0.129 | 0.181679512989 | 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 |
| S/T | rs764271138 |
0.071 | 0.22 | N | 0.39 | 0.129 | 0.181679512989 | gnomAD-4.0.0 | 5.57753E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.7812E-06 | 0 | 1.60118E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1077 | likely_benign | 0.1061 | benign | -0.435 | Destabilizing | 0.104 | N | 0.414 | neutral | N | 0.469439319 | None | None | I |
| S/C | 0.1344 | likely_benign | 0.1367 | benign | -0.244 | Destabilizing | 0.958 | D | 0.487 | neutral | N | 0.492178383 | None | None | I |
| S/D | 0.2965 | likely_benign | 0.2935 | benign | -0.065 | Destabilizing | 0.157 | N | 0.347 | neutral | None | None | None | None | I |
| S/E | 0.4784 | ambiguous | 0.4536 | ambiguous | -0.164 | Destabilizing | 0.272 | N | 0.367 | neutral | None | None | None | None | I |
| S/F | 0.1931 | likely_benign | 0.1779 | benign | -1.069 | Destabilizing | 0.002 | N | 0.363 | neutral | N | 0.463438612 | None | None | I |
| S/G | 0.1319 | likely_benign | 0.1274 | benign | -0.538 | Destabilizing | 0.272 | N | 0.363 | neutral | None | None | None | None | I |
| S/H | 0.3168 | likely_benign | 0.3217 | benign | -1.103 | Destabilizing | 0.726 | D | 0.433 | neutral | None | None | None | None | I |
| S/I | 0.2109 | likely_benign | 0.2123 | benign | -0.295 | Destabilizing | 0.396 | N | 0.623 | neutral | None | None | None | None | I |
| S/K | 0.6518 | likely_pathogenic | 0.6524 | pathogenic | -0.517 | Destabilizing | 0.272 | N | 0.349 | neutral | None | None | None | None | I |
| S/L | 0.1219 | likely_benign | 0.1192 | benign | -0.295 | Destabilizing | 0.157 | N | 0.536 | neutral | None | None | None | None | I |
| S/M | 0.1726 | likely_benign | 0.1697 | benign | 0.094 | Stabilizing | 0.909 | D | 0.435 | neutral | None | None | None | None | I |
| S/N | 0.1064 | likely_benign | 0.1009 | benign | -0.236 | Destabilizing | 0.005 | N | 0.256 | neutral | None | None | None | None | I |
| S/P | 0.8935 | likely_pathogenic | 0.9055 | pathogenic | -0.314 | Destabilizing | 0.859 | D | 0.432 | neutral | N | 0.50277422 | None | None | I |
| S/Q | 0.4949 | ambiguous | 0.4877 | ambiguous | -0.535 | Destabilizing | 0.726 | D | 0.339 | neutral | None | None | None | None | I |
| S/R | 0.6372 | likely_pathogenic | 0.6388 | pathogenic | -0.283 | Destabilizing | 0.726 | D | 0.439 | neutral | None | None | None | None | I |
| S/T | 0.0761 | likely_benign | 0.0762 | benign | -0.335 | Destabilizing | 0.22 | N | 0.39 | neutral | N | 0.47418652 | None | None | I |
| S/V | 0.2082 | likely_benign | 0.2088 | benign | -0.314 | Destabilizing | 0.396 | N | 0.529 | neutral | None | None | None | None | I |
| S/W | 0.3851 | ambiguous | 0.3753 | ambiguous | -1.062 | Destabilizing | 0.909 | D | 0.73 | prob.delet. | None | None | None | None | I |
| S/Y | 0.1713 | likely_benign | 0.167 | benign | -0.79 | Destabilizing | 0.331 | N | 0.631 | neutral | N | 0.486923744 | 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.