Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20247 | 60964;60965;60966 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| N2AB | 18606 | 56041;56042;56043 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| N2A | 17679 | 53260;53261;53262 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| N2B | 11182 | 33769;33770;33771 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| Novex-1 | 11307 | 34144;34145;34146 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| Novex-2 | 11374 | 34345;34346;34347 | chr2:178590986;178590985;178590984 | chr2:179455713;179455712;179455711 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/I | None | None | 0.497 | N | 0.697 | 0.221 | 0.274366138417 | gnomAD-4.0.0 | 6.84328E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9962E-07 | 0 | 0 |
| R/K | None | None | None | N | 0.318 | 0.119 | 0.0401082797425 | gnomAD-4.0.0 | 6.84328E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65678E-05 |
| R/T | rs1476856391  |
-1.473 | 0.124 | N | 0.564 | 0.215 | 0.183819452728 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/T | rs1476856391 |
-1.473 | 0.124 | N | 0.564 | 0.215 | 0.183819452728 | gnomAD-4.0.0 | 6.84328E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.1595E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6285 | likely_pathogenic | 0.6968 | pathogenic | -1.234 | Destabilizing | 0.072 | N | 0.608 | neutral | None | None | None | None | N |
| R/C | 0.2146 | likely_benign | 0.224 | benign | -1.244 | Destabilizing | 0.909 | D | 0.694 | prob.neutral | None | None | None | None | N |
| R/D | 0.9586 | likely_pathogenic | 0.9717 | pathogenic | -0.357 | Destabilizing | 0.567 | D | 0.627 | neutral | None | None | None | None | N |
| R/E | 0.6932 | likely_pathogenic | 0.7668 | pathogenic | -0.165 | Destabilizing | 0.157 | N | 0.663 | neutral | None | None | None | None | N |
| R/F | 0.6932 | likely_pathogenic | 0.7497 | pathogenic | -0.562 | Destabilizing | 0.726 | D | 0.709 | prob.delet. | None | None | None | None | N |
| R/G | 0.5792 | likely_pathogenic | 0.6477 | pathogenic | -1.612 | Destabilizing | 0.124 | N | 0.589 | neutral | N | 0.499983652 | None | None | N |
| R/H | 0.2033 | likely_benign | 0.2053 | benign | -1.618 | Destabilizing | 0.726 | D | 0.612 | neutral | None | None | None | None | N |
| R/I | 0.5173 | ambiguous | 0.6552 | pathogenic | -0.173 | Destabilizing | 0.497 | N | 0.697 | prob.neutral | N | 0.467938971 | None | None | N |
| R/K | 0.1147 | likely_benign | 0.1334 | benign | -1.137 | Destabilizing | None | N | 0.318 | neutral | N | 0.488273325 | None | None | N |
| R/L | 0.4643 | ambiguous | 0.5246 | ambiguous | -0.173 | Destabilizing | 0.272 | N | 0.577 | neutral | None | None | None | None | N |
| R/M | 0.3358 | likely_benign | 0.4072 | ambiguous | -0.66 | Destabilizing | 0.968 | D | 0.611 | neutral | None | None | None | None | N |
| R/N | 0.857 | likely_pathogenic | 0.8986 | pathogenic | -0.85 | Destabilizing | 0.157 | N | 0.621 | neutral | None | None | None | None | N |
| R/P | 0.9925 | likely_pathogenic | 0.9956 | pathogenic | -0.509 | Destabilizing | 0.726 | D | 0.667 | neutral | None | None | None | None | N |
| R/Q | 0.1468 | likely_benign | 0.1622 | benign | -0.799 | Destabilizing | 0.157 | N | 0.662 | neutral | None | None | None | None | N |
| R/S | 0.6415 | likely_pathogenic | 0.7042 | pathogenic | -1.68 | Destabilizing | 0.001 | N | 0.451 | neutral | N | 0.474845455 | None | None | N |
| R/T | 0.4302 | ambiguous | 0.5168 | ambiguous | -1.274 | Destabilizing | 0.124 | N | 0.564 | neutral | N | 0.466925013 | None | None | N |
| R/V | 0.5833 | likely_pathogenic | 0.6868 | pathogenic | -0.509 | Destabilizing | 0.567 | D | 0.671 | neutral | None | None | None | None | N |
| R/W | 0.3364 | likely_benign | 0.3818 | ambiguous | -0.101 | Destabilizing | 0.968 | D | 0.678 | prob.neutral | None | None | None | None | N |
| R/Y | 0.5899 | likely_pathogenic | 0.6362 | pathogenic | 0.104 | Stabilizing | 0.726 | D | 0.669 | 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.