Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22594 | 68005;68006;68007 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| N2AB | 20953 | 63082;63083;63084 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| N2A | 20026 | 60301;60302;60303 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| N2B | 13529 | 40810;40811;40812 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| Novex-1 | 13654 | 41185;41186;41187 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| Novex-2 | 13721 | 41386;41387;41388 | chr2:178579250;178579249;178579248 | chr2:179443977;179443976;179443975 |
| 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/V | rs369911767  |
0.193 | 0.949 | N | 0.565 | 0.237 | None | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 3.87747E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs369911767 |
0.193 | 0.949 | N | 0.565 | 0.237 | None | gnomAD-3.1.2 | 8.55E-05 | None | None | None | None | N | None | 2.89561E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs369911767 |
0.193 | 0.949 | N | 0.565 | 0.237 | None | gnomAD-4.0.0 | 1.36365E-05 | None | None | None | None | N | None | 2.80419E-04 | 1.6675E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.3445 | ambiguous | 0.3132 | benign | -0.126 | Destabilizing | 0.565 | D | 0.419 | neutral | N | 0.484973943 | None | None | N |
| D/C | 0.7942 | likely_pathogenic | 0.7713 | pathogenic | 0.22 | Stabilizing | 0.996 | D | 0.649 | neutral | None | None | None | None | N |
| D/E | 0.3681 | ambiguous | 0.35 | ambiguous | -0.207 | Destabilizing | 0.003 | N | 0.215 | neutral | N | 0.447282346 | None | None | N |
| D/F | 0.8538 | likely_pathogenic | 0.8269 | pathogenic | -0.274 | Destabilizing | 0.987 | D | 0.585 | neutral | None | None | None | None | N |
| D/G | 0.2081 | likely_benign | 0.1893 | benign | -0.268 | Destabilizing | 0.008 | N | 0.345 | neutral | N | 0.44943443 | None | None | N |
| D/H | 0.5178 | ambiguous | 0.4639 | ambiguous | -0.046 | Destabilizing | 0.986 | D | 0.393 | neutral | N | 0.504349137 | None | None | N |
| D/I | 0.7525 | likely_pathogenic | 0.7204 | pathogenic | 0.183 | Stabilizing | 0.961 | D | 0.587 | neutral | None | None | None | None | N |
| D/K | 0.6972 | likely_pathogenic | 0.6473 | pathogenic | 0.541 | Stabilizing | 0.633 | D | 0.388 | neutral | None | None | None | None | N |
| D/L | 0.6691 | likely_pathogenic | 0.6348 | pathogenic | 0.183 | Stabilizing | 0.923 | D | 0.589 | neutral | None | None | None | None | N |
| D/M | 0.8239 | likely_pathogenic | 0.788 | pathogenic | 0.296 | Stabilizing | 0.996 | D | 0.603 | neutral | None | None | None | None | N |
| D/N | 0.1263 | likely_benign | 0.1116 | benign | 0.353 | Stabilizing | 0.722 | D | 0.436 | neutral | N | 0.450263936 | None | None | N |
| D/P | 0.8574 | likely_pathogenic | 0.8299 | pathogenic | 0.1 | Stabilizing | 0.961 | D | 0.398 | neutral | None | None | None | None | N |
| D/Q | 0.6207 | likely_pathogenic | 0.5736 | pathogenic | 0.353 | Stabilizing | 0.858 | D | 0.407 | neutral | None | None | None | None | N |
| D/R | 0.7213 | likely_pathogenic | 0.6766 | pathogenic | 0.597 | Stabilizing | 0.923 | D | 0.527 | neutral | None | None | None | None | N |
| D/S | 0.161 | likely_benign | 0.1376 | benign | 0.261 | Stabilizing | 0.775 | D | 0.399 | neutral | None | None | None | None | N |
| D/T | 0.305 | likely_benign | 0.2541 | benign | 0.37 | Stabilizing | 0.775 | D | 0.377 | neutral | None | None | None | None | N |
| D/V | 0.5117 | ambiguous | 0.4918 | ambiguous | 0.1 | Stabilizing | 0.949 | D | 0.565 | neutral | N | 0.489611758 | None | None | N |
| D/W | 0.9711 | likely_pathogenic | 0.9622 | pathogenic | -0.222 | Destabilizing | 0.996 | D | 0.651 | neutral | None | None | None | None | N |
| D/Y | 0.5691 | likely_pathogenic | 0.5156 | ambiguous | -0.05 | Destabilizing | 0.983 | D | 0.584 | neutral | N | 0.458151331 | 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.