Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30976 | 93151;93152;93153 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| N2AB | 29335 | 88228;88229;88230 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| N2A | 28408 | 85447;85448;85449 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| N2B | 21911 | 65956;65957;65958 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| Novex-1 | 22036 | 66331;66332;66333 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| Novex-2 | 22103 | 66532;66533;66534 | chr2:178548700;178548699;178548698 | chr2:179413427;179413426;179413425 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | None | None | 0.892 | N | 0.391 | 0.139 | 0.0986583533028 | gnomAD-4.0.0 | 6.8419E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99459E-07 | 0 | 0 |
| D/N | rs777345218  |
-0.4 | 0.204 | N | 0.25 | 0.137 | 0.112648838833 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | N | None | 8.26E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs777345218 |
-0.4 | 0.204 | N | 0.25 | 0.137 | 0.112648838833 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs777345218 |
-0.4 | 0.204 | N | 0.25 | 0.137 | 0.112648838833 | gnomAD-4.0.0 | 5.12397E-06 | None | None | None | None | N | None | 6.76613E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | None | None | 0.056 | N | 0.441 | 0.256 | 0.375147631797 | gnomAD-4.0.0 | 1.59117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.8826E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1449 | likely_benign | 0.1502 | benign | -0.319 | Destabilizing | 0.892 | D | 0.495 | neutral | N | 0.492707992 | None | None | N |
| D/C | 0.6262 | likely_pathogenic | 0.6166 | pathogenic | -0.171 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| D/E | 0.1149 | likely_benign | 0.1312 | benign | -0.305 | Destabilizing | 0.892 | D | 0.391 | neutral | N | 0.396949527 | None | None | N |
| D/F | 0.6785 | likely_pathogenic | 0.689 | pathogenic | -0.098 | Destabilizing | 0.95 | D | 0.667 | neutral | None | None | None | None | N |
| D/G | 0.1631 | likely_benign | 0.1611 | benign | -0.515 | Destabilizing | 0.892 | D | 0.456 | neutral | N | 0.455434896 | None | None | N |
| D/H | 0.3353 | likely_benign | 0.333 | benign | 0.285 | Stabilizing | 0.967 | D | 0.505 | neutral | N | 0.487302172 | None | None | N |
| D/I | 0.4048 | ambiguous | 0.417 | ambiguous | 0.153 | Stabilizing | 0.975 | D | 0.665 | neutral | None | None | None | None | N |
| D/K | 0.3695 | ambiguous | 0.3791 | ambiguous | 0.323 | Stabilizing | 0.975 | D | 0.477 | neutral | None | None | None | None | N |
| D/L | 0.4203 | ambiguous | 0.4297 | ambiguous | 0.153 | Stabilizing | 0.95 | D | 0.671 | neutral | None | None | None | None | N |
| D/M | 0.6257 | likely_pathogenic | 0.6372 | pathogenic | 0.14 | Stabilizing | 0.999 | D | 0.666 | neutral | None | None | None | None | N |
| D/N | 0.1139 | likely_benign | 0.1141 | benign | -0.173 | Destabilizing | 0.204 | N | 0.25 | neutral | N | 0.437700071 | None | None | N |
| D/P | 0.4352 | ambiguous | 0.448 | ambiguous | 0.017 | Stabilizing | 0.996 | D | 0.495 | neutral | None | None | None | None | N |
| D/Q | 0.3339 | likely_benign | 0.3438 | ambiguous | -0.111 | Destabilizing | 0.987 | D | 0.429 | neutral | None | None | None | None | N |
| D/R | 0.4295 | ambiguous | 0.4212 | ambiguous | 0.602 | Stabilizing | 0.987 | D | 0.601 | neutral | None | None | None | None | N |
| D/S | 0.1177 | likely_benign | 0.1168 | benign | -0.241 | Destabilizing | 0.916 | D | 0.371 | neutral | None | None | None | None | N |
| D/T | 0.2362 | likely_benign | 0.2387 | benign | -0.075 | Destabilizing | 0.975 | D | 0.462 | neutral | None | None | None | None | N |
| D/V | 0.2362 | likely_benign | 0.2439 | benign | 0.017 | Stabilizing | 0.967 | D | 0.674 | neutral | N | 0.455833926 | None | None | N |
| D/W | 0.9019 | likely_pathogenic | 0.9044 | pathogenic | 0.084 | Stabilizing | 0.997 | D | 0.674 | neutral | None | None | None | None | N |
| D/Y | 0.3185 | likely_benign | 0.3201 | benign | 0.152 | Stabilizing | 0.056 | N | 0.441 | neutral | N | 0.506234649 | 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.