Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25419 | 76480;76481;76482 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| N2AB | 23778 | 71557;71558;71559 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| N2A | 22851 | 68776;68777;68778 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| N2B | 16354 | 49285;49286;49287 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| Novex-1 | 16479 | 49660;49661;49662 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| Novex-2 | 16546 | 49861;49862;49863 | chr2:178569877;178569876;178569875 | chr2:179434604;179434603;179434602 |
| 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/K | rs1427806281  |
-0.684 | 0.014 | N | 0.187 | 0.101 | 0.201204373187 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs1427806281 |
-0.684 | 0.014 | N | 0.187 | 0.101 | 0.201204373187 | gnomAD-4.0.0 | 1.59199E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43316E-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 | 0.3178 | likely_benign | 0.3287 | benign | -0.235 | Destabilizing | 0.559 | D | 0.619 | neutral | None | None | None | None | N |
| R/C | 0.1464 | likely_benign | 0.1575 | benign | -0.283 | Destabilizing | 0.043 | N | 0.533 | neutral | None | None | None | None | N |
| R/D | 0.6284 | likely_pathogenic | 0.6262 | pathogenic | -0.124 | Destabilizing | 0.956 | D | 0.647 | neutral | None | None | None | None | N |
| R/E | 0.3943 | ambiguous | 0.3972 | ambiguous | -0.064 | Destabilizing | 0.754 | D | 0.519 | neutral | None | None | None | None | N |
| R/F | 0.6361 | likely_pathogenic | 0.6434 | pathogenic | -0.452 | Destabilizing | 0.978 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/G | 0.2044 | likely_benign | 0.1973 | benign | -0.439 | Destabilizing | 0.822 | D | 0.633 | neutral | N | 0.451408448 | None | None | N |
| R/H | 0.1078 | likely_benign | 0.1096 | benign | -0.843 | Destabilizing | 0.993 | D | 0.511 | neutral | None | None | None | None | N |
| R/I | 0.3994 | ambiguous | 0.4082 | ambiguous | 0.271 | Stabilizing | 0.942 | D | 0.708 | prob.delet. | N | 0.505763008 | None | None | N |
| R/K | 0.0894 | likely_benign | 0.0924 | benign | -0.279 | Destabilizing | 0.014 | N | 0.187 | neutral | N | 0.414044925 | None | None | N |
| R/L | 0.312 | likely_benign | 0.3169 | benign | 0.271 | Stabilizing | 0.754 | D | 0.632 | neutral | None | None | None | None | N |
| R/M | 0.3619 | ambiguous | 0.3637 | ambiguous | -0.005 | Destabilizing | 0.998 | D | 0.6 | neutral | None | None | None | None | N |
| R/N | 0.4683 | ambiguous | 0.4614 | ambiguous | 0.09 | Stabilizing | 0.956 | D | 0.523 | neutral | None | None | None | None | N |
| R/P | 0.43 | ambiguous | 0.3996 | ambiguous | 0.123 | Stabilizing | 0.978 | D | 0.697 | prob.neutral | None | None | None | None | N |
| R/Q | 0.1116 | likely_benign | 0.1114 | benign | -0.102 | Destabilizing | 0.956 | D | 0.586 | neutral | None | None | None | None | N |
| R/S | 0.3796 | ambiguous | 0.3852 | ambiguous | -0.389 | Destabilizing | 0.822 | D | 0.628 | neutral | N | 0.409404323 | None | None | N |
| R/T | 0.2845 | likely_benign | 0.276 | benign | -0.193 | Destabilizing | 0.822 | D | 0.617 | neutral | N | 0.503682708 | None | None | N |
| R/V | 0.4503 | ambiguous | 0.4561 | ambiguous | 0.123 | Stabilizing | 0.956 | D | 0.647 | neutral | None | None | None | None | N |
| R/W | 0.2877 | likely_benign | 0.2833 | benign | -0.402 | Destabilizing | 0.998 | D | 0.791 | deleterious | None | None | None | None | N |
| R/Y | 0.404 | ambiguous | 0.4084 | ambiguous | -0.014 | Destabilizing | 0.993 | D | 0.692 | 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.