Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31704 | 95335;95336;95337 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| N2AB | 30063 | 90412;90413;90414 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| N2A | 29136 | 87631;87632;87633 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| N2B | 22639 | 68140;68141;68142 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| Novex-1 | 22764 | 68515;68516;68517 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| Novex-2 | 22831 | 68716;68717;68718 | chr2:178546221;178546220;178546219 | chr2:179410948;179410947;179410946 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs754379972  |
0.092 | 0.999 | N | 0.618 | 0.355 | 0.538468847496 | gnomAD-2.1.1 | 8.13E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.67E-05 | None | 0 | 0 | 0 |
| K/R | rs754379972 |
0.092 | 0.999 | N | 0.618 | 0.355 | 0.538468847496 | gnomAD-4.0.0 | 4.81439E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 4.33438E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.6176 | likely_pathogenic | 0.7431 | pathogenic | -0.28 | Destabilizing | 0.999 | D | 0.707 | prob.neutral | None | None | None | None | I |
| K/C | 0.7501 | likely_pathogenic | 0.841 | pathogenic | -0.511 | Destabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| K/D | 0.8139 | likely_pathogenic | 0.8785 | pathogenic | 0.389 | Stabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| K/E | 0.345 | ambiguous | 0.4827 | ambiguous | 0.472 | Stabilizing | 0.999 | D | 0.677 | prob.neutral | N | 0.491615566 | None | None | I |
| K/F | 0.9096 | likely_pathogenic | 0.9544 | pathogenic | -0.133 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| K/G | 0.813 | likely_pathogenic | 0.8879 | pathogenic | -0.584 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| K/H | 0.3495 | ambiguous | 0.4341 | ambiguous | -0.758 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| K/I | 0.5514 | ambiguous | 0.7026 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | N | 0.505027581 | None | None | I |
| K/L | 0.5356 | ambiguous | 0.6721 | pathogenic | 0.475 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
| K/M | 0.3539 | ambiguous | 0.4731 | ambiguous | 0.144 | Stabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| K/N | 0.5916 | likely_pathogenic | 0.7061 | pathogenic | -0.123 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | D | 0.528923161 | None | None | I |
| K/P | 0.9867 | likely_pathogenic | 0.9903 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| K/Q | 0.1817 | likely_benign | 0.2558 | benign | -0.183 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | D | 0.52376527 | None | None | I |
| K/R | 0.093 | likely_benign | 0.1057 | benign | -0.225 | Destabilizing | 0.999 | D | 0.618 | neutral | N | 0.483209514 | None | None | I |
| K/S | 0.6204 | likely_pathogenic | 0.7514 | pathogenic | -0.783 | Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | I |
| K/T | 0.2442 | likely_benign | 0.341 | ambiguous | -0.505 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.498194822 | None | None | I |
| K/V | 0.4833 | ambiguous | 0.6273 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| K/W | 0.864 | likely_pathogenic | 0.9201 | pathogenic | -0.047 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| K/Y | 0.7898 | likely_pathogenic | 0.8643 | pathogenic | 0.268 | Stabilizing | 1.0 | D | 0.71 | 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.