Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15581 | 46966;46967;46968 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| N2AB | 13940 | 42043;42044;42045 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| N2A | 13013 | 39262;39263;39264 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| N2B | 6516 | 19771;19772;19773 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| Novex-1 | 6641 | 20146;20147;20148 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| Novex-2 | 6708 | 20347;20348;20349 | chr2:178618809;178618808;178618807 | chr2:179483536;179483535;179483534 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs767913696  |
-0.455 | None | N | 0.167 | 0.111 | 0.15556083564 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| V/A | rs767913696 |
-0.455 | None | N | 0.167 | 0.111 | 0.15556083564 | gnomAD-4.0.0 | 4.11268E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00275E-07 | 5.80707E-05 | 0 |
| V/G | None | None | 0.124 | N | 0.444 | 0.104 | 0.332386209738 | gnomAD-4.0.0 | 6.85447E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00275E-07 | 0 | 0 |
| V/I | rs2057792171 |
None | 0.104 | N | 0.404 | 0.128 | 0.279776271856 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| V/I | rs2057792171 |
None | 0.104 | N | 0.404 | 0.128 | 0.279776271856 | gnomAD-4.0.0 | 6.58233E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.40911E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0663 | likely_benign | 0.0923 | benign | -0.929 | Destabilizing | None | N | 0.167 | neutral | N | 0.415320593 | None | None | I |
| V/C | 0.543 | ambiguous | 0.6649 | pathogenic | -0.611 | Destabilizing | 0.909 | D | 0.383 | neutral | None | None | None | None | I |
| V/D | 0.345 | ambiguous | 0.4821 | ambiguous | -0.81 | Destabilizing | 0.497 | N | 0.547 | neutral | N | 0.458506101 | None | None | I |
| V/E | 0.2324 | likely_benign | 0.3089 | benign | -0.898 | Destabilizing | 0.567 | D | 0.451 | neutral | None | None | None | None | I |
| V/F | 0.2061 | likely_benign | 0.2738 | benign | -0.932 | Destabilizing | 0.667 | D | 0.364 | neutral | N | 0.458506101 | None | None | I |
| V/G | 0.1841 | likely_benign | 0.253 | benign | -1.133 | Destabilizing | 0.124 | N | 0.444 | neutral | N | 0.459499803 | None | None | I |
| V/H | 0.5108 | ambiguous | 0.6416 | pathogenic | -0.692 | Destabilizing | 0.968 | D | 0.564 | neutral | None | None | None | None | I |
| V/I | 0.0872 | likely_benign | 0.1012 | benign | -0.514 | Destabilizing | 0.104 | N | 0.404 | neutral | N | 0.454505364 | None | None | I |
| V/K | 0.3162 | likely_benign | 0.3697 | ambiguous | -0.856 | Destabilizing | 0.567 | D | 0.451 | neutral | None | None | None | None | I |
| V/L | 0.2248 | likely_benign | 0.3208 | benign | -0.514 | Destabilizing | 0.055 | N | 0.416 | neutral | N | 0.452238203 | None | None | I |
| V/M | 0.1349 | likely_benign | 0.2013 | benign | -0.363 | Destabilizing | 0.726 | D | 0.365 | neutral | None | None | None | None | I |
| V/N | 0.2277 | likely_benign | 0.324 | benign | -0.501 | Destabilizing | 0.726 | D | 0.563 | neutral | None | None | None | None | I |
| V/P | 0.6763 | likely_pathogenic | 0.7786 | pathogenic | -0.617 | Destabilizing | 0.567 | D | 0.485 | neutral | None | None | None | None | I |
| V/Q | 0.2786 | likely_benign | 0.3538 | ambiguous | -0.769 | Destabilizing | 0.726 | D | 0.514 | neutral | None | None | None | None | I |
| V/R | 0.293 | likely_benign | 0.3396 | benign | -0.254 | Destabilizing | 0.567 | D | 0.553 | neutral | None | None | None | None | I |
| V/S | 0.1152 | likely_benign | 0.1628 | benign | -0.886 | Destabilizing | 0.157 | N | 0.423 | neutral | None | None | None | None | I |
| V/T | 0.1076 | likely_benign | 0.1517 | benign | -0.879 | Destabilizing | 0.157 | N | 0.321 | neutral | None | None | None | None | I |
| V/W | 0.8126 | likely_pathogenic | 0.8938 | pathogenic | -1.032 | Destabilizing | 0.968 | D | 0.658 | neutral | None | None | None | None | I |
| V/Y | 0.5146 | ambiguous | 0.6461 | pathogenic | -0.765 | Destabilizing | 0.726 | D | 0.367 | neutral | None | None | None | None | I |
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.