Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14990 | 45193;45194;45195 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| N2AB | 13349 | 40270;40271;40272 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| N2A | 12422 | 37489;37490;37491 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| N2B | 5925 | 17998;17999;18000 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| Novex-1 | 6050 | 18373;18374;18375 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| Novex-2 | 6117 | 18574;18575;18576 | chr2:178621954;178621953;178621952 | chr2:179486681;179486680;179486679 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | rs751709104  |
-0.189 | 0.889 | N | 0.296 | 0.122 | 0.587841187436 | gnomAD-2.1.1 | 2.03E-05 | None | None | None | None | N | None | 0 | 1.46293E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/L | rs751709104 |
-0.189 | 0.889 | N | 0.296 | 0.122 | 0.587841187436 | gnomAD-4.0.0 | 1.11756E-05 | None | None | None | None | N | None | 0 | 1.60927E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs766807618 |
-0.325 | 0.998 | D | 0.536 | 0.256 | 0.53586618445 | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | N | None | 0 | 8.57E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.41764E-04 |
| I/M | rs766807618 |
-0.325 | 0.998 | D | 0.536 | 0.256 | 0.53586618445 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/M | rs766807618 |
-0.325 | 0.998 | D | 0.536 | 0.256 | 0.53586618445 | gnomAD-4.0.0 | 6.42431E-06 | None | None | None | None | N | None | 0 | 8.51644E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6988 | likely_pathogenic | 0.7402 | pathogenic | -1.531 | Destabilizing | 0.992 | D | 0.463 | neutral | None | None | None | None | N |
| I/C | 0.9079 | likely_pathogenic | 0.9176 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | N |
| I/D | 0.907 | likely_pathogenic | 0.9309 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/E | 0.8155 | likely_pathogenic | 0.8602 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| I/F | 0.2576 | likely_benign | 0.2886 | benign | -1.073 | Destabilizing | 0.999 | D | 0.54 | neutral | None | None | None | None | N |
| I/G | 0.918 | likely_pathogenic | 0.9336 | pathogenic | -1.837 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| I/H | 0.7256 | likely_pathogenic | 0.7766 | pathogenic | -1.033 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | N |
| I/K | 0.716 | likely_pathogenic | 0.7824 | pathogenic | -1.123 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | N | 0.501364396 | None | None | N |
| I/L | 0.1851 | likely_benign | 0.217 | benign | -0.772 | Destabilizing | 0.889 | D | 0.296 | neutral | N | 0.506260971 | None | None | N |
| I/M | 0.239 | likely_benign | 0.2659 | benign | -0.546 | Destabilizing | 0.998 | D | 0.536 | neutral | D | 0.566292962 | None | None | N |
| I/N | 0.5867 | likely_pathogenic | 0.6489 | pathogenic | -0.914 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/P | 0.9676 | likely_pathogenic | 0.9743 | pathogenic | -0.993 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| I/Q | 0.6746 | likely_pathogenic | 0.7484 | pathogenic | -1.107 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/R | 0.6259 | likely_pathogenic | 0.6975 | pathogenic | -0.477 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | N | 0.50551196 | None | None | N |
| I/S | 0.5789 | likely_pathogenic | 0.63 | pathogenic | -1.464 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| I/T | 0.5044 | ambiguous | 0.5459 | ambiguous | -1.364 | Destabilizing | 0.989 | D | 0.509 | neutral | N | 0.493378928 | None | None | N |
| I/V | 0.1493 | likely_benign | 0.1484 | benign | -0.993 | Destabilizing | 0.333 | N | 0.205 | neutral | N | 0.506471366 | None | None | N |
| I/W | 0.8999 | likely_pathogenic | 0.921 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.635 | neutral | None | None | None | None | N |
| I/Y | 0.674 | likely_pathogenic | 0.714 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.609 | 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.