Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28364 | 85315;85316;85317 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| N2AB | 26723 | 80392;80393;80394 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| N2A | 25796 | 77611;77612;77613 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| N2B | 19299 | 58120;58121;58122 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| Novex-1 | 19424 | 58495;58496;58497 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| Novex-2 | 19491 | 58696;58697;58698 | chr2:178561042;178561041;178561040 | chr2:179425769;179425768;179425767 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | None | None | 0.957 | N | 0.403 | 0.385 | 0.37479162749 | gnomAD-4.0.0 | 6.84175E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99446E-07 | 0 | 0 |
| R/Q | rs376283153  |
-0.007 | 0.175 | D | 0.186 | 0.14 | None | gnomAD-2.1.1 | 1.50035E-04 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 1.89491E-03 | None | 6.54E-05 | None | 0 | 0 | 1.40371E-04 |
| R/Q | rs376283153 |
-0.007 | 0.175 | D | 0.186 | 0.14 | None | gnomAD-3.1.2 | 1.44617E-04 | None | None | None | None | N | None | 2.41E-05 | 7.20839E-04 | 0 | 0 | 1.73544E-03 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs376283153 |
-0.007 | 0.175 | D | 0.186 | 0.14 | None | gnomAD-4.0.0 | 4.77152E-05 | None | None | None | None | N | None | 4.00502E-05 | 2.00067E-04 | None | 0 | 1.00263E-03 | None | 1.56216E-05 | 0 | 5.93309E-06 | 3.29395E-05 | 9.60646E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5992 | likely_pathogenic | 0.549 | ambiguous | 0.003 | Stabilizing | 0.25 | N | 0.362 | neutral | None | None | None | None | N |
| R/C | 0.3342 | likely_benign | 0.3032 | benign | -0.161 | Destabilizing | 0.992 | D | 0.43 | neutral | None | None | None | None | N |
| R/D | 0.8517 | likely_pathogenic | 0.8273 | pathogenic | -0.127 | Destabilizing | 0.85 | D | 0.361 | neutral | None | None | None | None | N |
| R/E | 0.5646 | likely_pathogenic | 0.5254 | ambiguous | -0.073 | Destabilizing | 0.447 | N | 0.371 | neutral | None | None | None | None | N |
| R/F | 0.8166 | likely_pathogenic | 0.7808 | pathogenic | -0.253 | Destabilizing | 0.85 | D | 0.396 | neutral | None | None | None | None | N |
| R/G | 0.3699 | ambiguous | 0.327 | benign | -0.173 | Destabilizing | 0.756 | D | 0.372 | neutral | N | 0.515220358 | None | None | N |
| R/H | 0.1721 | likely_benign | 0.1537 | benign | -0.629 | Destabilizing | 0.92 | D | 0.367 | neutral | None | None | None | None | N |
| R/I | 0.554 | ambiguous | 0.5069 | ambiguous | 0.429 | Stabilizing | 0.012 | N | 0.331 | neutral | None | None | None | None | N |
| R/K | 0.1493 | likely_benign | 0.1372 | benign | -0.08 | Destabilizing | 0.021 | N | 0.181 | neutral | None | None | None | None | N |
| R/L | 0.4123 | ambiguous | 0.3785 | ambiguous | 0.429 | Stabilizing | 0.348 | N | 0.365 | neutral | D | 0.522858406 | None | None | N |
| R/M | 0.473 | ambiguous | 0.4388 | ambiguous | 0.034 | Stabilizing | 0.85 | D | 0.366 | neutral | None | None | None | None | N |
| R/N | 0.7648 | likely_pathogenic | 0.723 | pathogenic | 0.124 | Stabilizing | 0.617 | D | 0.373 | neutral | None | None | None | None | N |
| R/P | 0.8003 | likely_pathogenic | 0.7893 | pathogenic | 0.307 | Stabilizing | 0.957 | D | 0.403 | neutral | N | 0.485764243 | None | None | N |
| R/Q | 0.1482 | likely_benign | 0.1436 | benign | 0.023 | Stabilizing | 0.175 | N | 0.186 | neutral | D | 0.527013432 | None | None | N |
| R/S | 0.6749 | likely_pathogenic | 0.6242 | pathogenic | -0.195 | Destabilizing | 0.447 | N | 0.332 | neutral | None | None | None | None | N |
| R/T | 0.3989 | ambiguous | 0.3647 | ambiguous | -0.017 | Destabilizing | 0.617 | D | 0.366 | neutral | None | None | None | None | N |
| R/V | 0.6547 | likely_pathogenic | 0.6095 | pathogenic | 0.307 | Stabilizing | 0.217 | N | 0.363 | neutral | None | None | None | None | N |
| R/W | 0.2514 | likely_benign | 0.24 | benign | -0.337 | Destabilizing | 0.992 | D | 0.508 | neutral | None | None | None | None | N |
| R/Y | 0.6275 | likely_pathogenic | 0.5847 | pathogenic | 0.074 | Stabilizing | 0.92 | D | 0.398 | 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.