Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14426 | 43501;43502;43503 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| N2AB | 12785 | 38578;38579;38580 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| N2A | 11858 | 35797;35798;35799 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| N2B | 5361 | 16306;16307;16308 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| Novex-1 | 5486 | 16681;16682;16683 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| Novex-2 | 5553 | 16882;16883;16884 | chr2:178632730;178632729;178632728 | chr2:179497457;179497456;179497455 |
| 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/E | rs557077441  |
0.171 | 0.822 | N | 0.556 | 0.424 | 0.305730143919 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.96155E-04 | None | 0 | 0 | 0 |
| K/E | rs557077441 |
0.171 | 0.822 | N | 0.556 | 0.424 | 0.305730143919 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07297E-04 | 0 |
| K/E | rs557077441 |
0.171 | 0.822 | N | 0.556 | 0.424 | 0.305730143919 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| K/E | rs557077441 |
0.171 | 0.822 | N | 0.556 | 0.424 | 0.305730143919 | gnomAD-4.0.0 | 5.57856E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 7.68741E-05 | 3.20205E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.3873 | ambiguous | 0.393 | ambiguous | -0.736 | Destabilizing | 0.86 | D | 0.567 | neutral | None | None | None | None | N |
| K/C | 0.6775 | likely_pathogenic | 0.6648 | pathogenic | -0.772 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| K/D | 0.7879 | likely_pathogenic | 0.7785 | pathogenic | -0.068 | Destabilizing | 0.956 | D | 0.694 | prob.neutral | None | None | None | None | N |
| K/E | 0.2318 | likely_benign | 0.2359 | benign | 0.078 | Stabilizing | 0.822 | D | 0.556 | neutral | N | 0.411732579 | None | None | N |
| K/F | 0.7458 | likely_pathogenic | 0.7452 | pathogenic | -0.387 | Destabilizing | 0.998 | D | 0.711 | prob.delet. | None | None | None | None | N |
| K/G | 0.5973 | likely_pathogenic | 0.5844 | pathogenic | -1.111 | Destabilizing | 0.956 | D | 0.656 | neutral | None | None | None | None | N |
| K/H | 0.3181 | likely_benign | 0.3015 | benign | -1.243 | Destabilizing | 0.994 | D | 0.675 | neutral | None | None | None | None | N |
| K/I | 0.2266 | likely_benign | 0.2543 | benign | 0.248 | Stabilizing | 0.978 | D | 0.728 | prob.delet. | None | None | None | None | N |
| K/L | 0.3265 | likely_benign | 0.3453 | ambiguous | 0.248 | Stabilizing | 0.956 | D | 0.656 | neutral | None | None | None | None | N |
| K/M | 0.2216 | likely_benign | 0.2286 | benign | -0.025 | Destabilizing | 0.997 | D | 0.666 | neutral | D | 0.53005727 | None | None | N |
| K/N | 0.5167 | ambiguous | 0.5366 | ambiguous | -0.618 | Destabilizing | 0.942 | D | 0.629 | neutral | N | 0.497292219 | None | None | N |
| K/P | 0.9418 | likely_pathogenic | 0.9274 | pathogenic | -0.051 | Destabilizing | 0.993 | D | 0.692 | prob.neutral | None | None | None | None | N |
| K/Q | 0.1612 | likely_benign | 0.1606 | benign | -0.586 | Destabilizing | 0.942 | D | 0.647 | neutral | N | 0.51099583 | None | None | N |
| K/R | 0.0741 | likely_benign | 0.071 | benign | -0.47 | Destabilizing | 0.006 | N | 0.283 | neutral | N | 0.353534598 | None | None | N |
| K/S | 0.4624 | ambiguous | 0.4729 | ambiguous | -1.304 | Destabilizing | 0.86 | D | 0.579 | neutral | None | None | None | None | N |
| K/T | 0.1497 | likely_benign | 0.1571 | benign | -0.933 | Destabilizing | 0.942 | D | 0.681 | prob.neutral | N | 0.419737163 | None | None | N |
| K/V | 0.2155 | likely_benign | 0.2354 | benign | -0.051 | Destabilizing | 0.978 | D | 0.708 | prob.delet. | None | None | None | None | N |
| K/W | 0.7575 | likely_pathogenic | 0.7169 | pathogenic | -0.27 | Destabilizing | 0.998 | D | 0.64 | neutral | None | None | None | None | N |
| K/Y | 0.6248 | likely_pathogenic | 0.6172 | pathogenic | 0.02 | Stabilizing | 0.993 | D | 0.704 | prob.neutral | 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.