Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22962 | 69109;69110;69111 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| N2AB | 21321 | 64186;64187;64188 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| N2A | 20394 | 61405;61406;61407 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| N2B | 13897 | 41914;41915;41916 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| Novex-1 | 14022 | 42289;42290;42291 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| Novex-2 | 14089 | 42490;42491;42492 | chr2:178577451;178577450;178577449 | chr2:179442178;179442177;179442176 |
| 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/A | None | None | 0.124 | N | 0.526 | 0.216 | 0.224531998449 | gnomAD-4.0.0 | 1.61509E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.90897E-06 | 0 | 0 |
| D/Y | None | None | 0.859 | N | 0.597 | 0.353 | 0.455081427078 | gnomAD-4.0.0 | 6.88569E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0435E-07 | 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 | 0.2343 | likely_benign | 0.1951 | benign | -0.422 | Destabilizing | 0.124 | N | 0.526 | neutral | N | 0.50194355 | None | None | I |
| D/C | 0.7297 | likely_pathogenic | 0.6636 | pathogenic | 0.042 | Stabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | I |
| D/E | 0.1405 | likely_benign | 0.1154 | benign | -0.363 | Destabilizing | 0.001 | N | 0.213 | neutral | N | 0.434656979 | None | None | I |
| D/F | 0.7865 | likely_pathogenic | 0.7427 | pathogenic | -0.283 | Destabilizing | 0.726 | D | 0.598 | neutral | None | None | None | None | I |
| D/G | 0.2354 | likely_benign | 0.1985 | benign | -0.654 | Destabilizing | 0.001 | N | 0.271 | neutral | N | 0.458614061 | None | None | I |
| D/H | 0.4195 | ambiguous | 0.3526 | ambiguous | -0.267 | Destabilizing | 0.883 | D | 0.464 | neutral | N | 0.504079779 | None | None | I |
| D/I | 0.614 | likely_pathogenic | 0.5635 | ambiguous | 0.153 | Stabilizing | 0.567 | D | 0.592 | neutral | None | None | None | None | I |
| D/K | 0.4375 | ambiguous | 0.3602 | ambiguous | 0.272 | Stabilizing | 0.157 | N | 0.467 | neutral | None | None | None | None | I |
| D/L | 0.6222 | likely_pathogenic | 0.5624 | ambiguous | 0.153 | Stabilizing | 0.396 | N | 0.553 | neutral | None | None | None | None | I |
| D/M | 0.7001 | likely_pathogenic | 0.6227 | pathogenic | 0.414 | Stabilizing | 0.968 | D | 0.611 | neutral | None | None | None | None | I |
| D/N | 0.1058 | likely_benign | 0.097 | benign | -0.121 | Destabilizing | 0.22 | N | 0.458 | neutral | N | 0.485435303 | None | None | I |
| D/P | 0.9686 | likely_pathogenic | 0.9559 | pathogenic | -0.016 | Destabilizing | 0.726 | D | 0.464 | neutral | None | None | None | None | I |
| D/Q | 0.3522 | ambiguous | 0.2833 | benign | -0.072 | Destabilizing | 0.396 | N | 0.407 | neutral | None | None | None | None | I |
| D/R | 0.5661 | likely_pathogenic | 0.4821 | ambiguous | 0.4 | Stabilizing | 0.396 | N | 0.56 | neutral | None | None | None | None | I |
| D/S | 0.144 | likely_benign | 0.1201 | benign | -0.238 | Destabilizing | 0.157 | N | 0.437 | neutral | None | None | None | None | I |
| D/T | 0.3128 | likely_benign | 0.2634 | benign | -0.05 | Destabilizing | 0.003 | N | 0.302 | neutral | None | None | None | None | I |
| D/V | 0.4014 | ambiguous | 0.3612 | ambiguous | -0.016 | Destabilizing | 0.331 | N | 0.536 | neutral | N | 0.510795107 | None | None | I |
| D/W | 0.9556 | likely_pathogenic | 0.9406 | pathogenic | -0.108 | Destabilizing | 0.968 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/Y | 0.38 | ambiguous | 0.3464 | ambiguous | -0.032 | Destabilizing | 0.859 | D | 0.597 | neutral | N | 0.45930342 | 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.