Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19895 | 59908;59909;59910 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| N2AB | 18254 | 54985;54986;54987 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| N2A | 17327 | 52204;52205;52206 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| N2B | 10830 | 32713;32714;32715 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| Novex-1 | 10955 | 33088;33089;33090 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| Novex-2 | 11022 | 33289;33290;33291 | chr2:178592221;178592220;178592219 | chr2:179456948;179456947;179456946 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1355833226  |
None | 1.0 | N | 0.695 | 0.462 | None | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.1E-06 | 0 |
| Y/C | rs1355833226 |
None | 1.0 | N | 0.695 | 0.462 | None | gnomAD-4.0.0 | 4.78857E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.5951E-06 | 0 | 0 |
| Y/S | rs1355833226 |
None | 0.994 | N | 0.657 | 0.521 | 0.557792573389 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/S | rs1355833226 |
None | 0.994 | N | 0.657 | 0.521 | 0.557792573389 | gnomAD-4.0.0 | 2.56883E-06 | None | None | None | None | N | None | 3.38455E-05 | 0 | None | 0 | 0 | None | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.6532 | likely_pathogenic | 0.6662 | pathogenic | -2.443 | Highly Destabilizing | 0.983 | D | 0.582 | neutral | None | None | None | None | N |
| Y/C | 0.2217 | likely_benign | 0.2228 | benign | -1.057 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | N | 0.477672329 | None | None | N |
| Y/D | 0.7407 | likely_pathogenic | 0.7443 | pathogenic | -1.01 | Destabilizing | 0.994 | D | 0.725 | prob.delet. | N | 0.483982226 | None | None | N |
| Y/E | 0.8688 | likely_pathogenic | 0.871 | pathogenic | -0.89 | Destabilizing | 0.967 | D | 0.598 | neutral | None | None | None | None | N |
| Y/F | 0.1091 | likely_benign | 0.1055 | benign | -0.954 | Destabilizing | 0.996 | D | 0.45 | neutral | N | 0.490254837 | None | None | N |
| Y/G | 0.7092 | likely_pathogenic | 0.7342 | pathogenic | -2.784 | Highly Destabilizing | 0.998 | D | 0.687 | prob.neutral | None | None | None | None | N |
| Y/H | 0.2825 | likely_benign | 0.2924 | benign | -1.078 | Destabilizing | 0.997 | D | 0.618 | neutral | N | 0.493332428 | None | None | N |
| Y/I | 0.5103 | ambiguous | 0.5063 | ambiguous | -1.383 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| Y/K | 0.7633 | likely_pathogenic | 0.7792 | pathogenic | -1.114 | Destabilizing | 0.99 | D | 0.657 | neutral | None | None | None | None | N |
| Y/L | 0.454 | ambiguous | 0.4489 | ambiguous | -1.383 | Destabilizing | 0.983 | D | 0.535 | neutral | None | None | None | None | N |
| Y/M | 0.6178 | likely_pathogenic | 0.6329 | pathogenic | -1.056 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| Y/N | 0.3613 | ambiguous | 0.3771 | ambiguous | -1.445 | Destabilizing | 0.997 | D | 0.711 | prob.delet. | N | 0.463876313 | None | None | N |
| Y/P | 0.976 | likely_pathogenic | 0.9781 | pathogenic | -1.736 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| Y/Q | 0.6129 | likely_pathogenic | 0.6383 | pathogenic | -1.37 | Destabilizing | 0.84 | D | 0.373 | neutral | None | None | None | None | N |
| Y/R | 0.5658 | likely_pathogenic | 0.5861 | pathogenic | -0.682 | Destabilizing | 0.995 | D | 0.703 | prob.neutral | None | None | None | None | N |
| Y/S | 0.3415 | ambiguous | 0.3573 | ambiguous | -2.081 | Highly Destabilizing | 0.994 | D | 0.657 | neutral | N | 0.44777071 | None | None | N |
| Y/T | 0.5274 | ambiguous | 0.561 | ambiguous | -1.864 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| Y/V | 0.4307 | ambiguous | 0.4329 | ambiguous | -1.736 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | N |
| Y/W | 0.5299 | ambiguous | 0.5235 | ambiguous | -0.392 | Destabilizing | 1.0 | D | 0.605 | 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.