Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8777 | 26554;26555;26556 | chr2:178714445;178714444;178714443 | chr2:179579172;179579171;179579170 |
| N2AB | 8460 | 25603;25604;25605 | chr2:178714445;178714444;178714443 | chr2:179579172;179579171;179579170 |
| N2A | 7533 | 22822;22823;22824 | chr2:178714445;178714444;178714443 | chr2:179579172;179579171;179579170 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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/D | None | None | 0.908 | N | 0.444 | 0.519 | 0.846757116288 | gnomAD-4.0.0 | 1.59157E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85873E-06 | 0 | 0 |
| V/F | rs376823283  |
-0.593 | 0.754 | N | 0.359 | 0.38 | 0.787097682969 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/F | rs376823283 |
-0.593 | 0.754 | N | 0.359 | 0.38 | 0.787097682969 | gnomAD-4.0.0 | 2.73711E-06 | None | None | None | None | N | None | 0 | 4.47387E-05 | None | 0 | 0 | None | 0 | 0 | 1.79906E-06 | 0 | 0 |
| V/I | None | -0.026 | None | N | 0.145 | 0.064 | None | gnomAD-2.1.1 | 6.8E-05 | None | None | None | None | N | None | 4.14E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.33578E-04 | 0 |
| V/I | None | -0.026 | None | N | 0.145 | 0.064 | None | gnomAD-3.1.2 | 1.44585E-04 | None | None | None | None | N | None | 9.65E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 2.49941E-04 | 0 | 0 |
| V/I | None | -0.026 | None | N | 0.145 | 0.064 | None | gnomAD-4.0.0 | 1.19612E-04 | None | None | None | None | N | None | 6.67485E-05 | 3.33467E-05 | None | 0 | 0 | None | 1.56284E-05 | 0 | 1.53428E-04 | 0 | 6.40574E-05 |
| V/L | rs376823283 |
None | None | N | 0.127 | 0.122 | 0.312306559268 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78469E-04 |
| V/L | rs376823283 |
None | None | N | 0.127 | 0.122 | 0.312306559268 | gnomAD-4.0.0 | 1.85925E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69533E-06 | 0 | 1.60143E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2838 | likely_benign | 0.374 | ambiguous | -1.741 | Destabilizing | 0.071 | N | 0.283 | neutral | N | 0.488494395 | None | None | N |
| V/C | 0.784 | likely_pathogenic | 0.8442 | pathogenic | -1.158 | Destabilizing | 0.953 | D | 0.37 | neutral | None | None | None | None | N |
| V/D | 0.7039 | likely_pathogenic | 0.7939 | pathogenic | -2.525 | Highly Destabilizing | 0.908 | D | 0.444 | neutral | N | 0.49791537 | None | None | N |
| V/E | 0.5172 | ambiguous | 0.6138 | pathogenic | -2.265 | Highly Destabilizing | 0.679 | D | 0.41 | neutral | None | None | None | None | N |
| V/F | 0.192 | likely_benign | 0.2342 | benign | -1.093 | Destabilizing | 0.754 | D | 0.359 | neutral | N | 0.493685408 | None | None | N |
| V/G | 0.3949 | ambiguous | 0.4946 | ambiguous | -2.259 | Highly Destabilizing | 0.815 | D | 0.427 | neutral | N | 0.506055672 | None | None | N |
| V/H | 0.767 | likely_pathogenic | 0.8273 | pathogenic | -2.006 | Highly Destabilizing | 0.964 | D | 0.468 | neutral | None | None | None | None | N |
| V/I | 0.0735 | likely_benign | 0.0735 | benign | -0.273 | Destabilizing | None | N | 0.145 | neutral | N | 0.457654922 | None | None | N |
| V/K | 0.6303 | likely_pathogenic | 0.7161 | pathogenic | -1.489 | Destabilizing | 0.603 | D | 0.398 | neutral | None | None | None | None | N |
| V/L | 0.1284 | likely_benign | 0.1474 | benign | -0.273 | Destabilizing | None | N | 0.127 | neutral | N | 0.44368276 | None | None | N |
| V/M | 0.152 | likely_benign | 0.178 | benign | -0.324 | Destabilizing | 0.533 | D | 0.399 | neutral | None | None | None | None | N |
| V/N | 0.5906 | likely_pathogenic | 0.6825 | pathogenic | -2.003 | Highly Destabilizing | 0.407 | N | 0.441 | neutral | None | None | None | None | N |
| V/P | 0.6758 | likely_pathogenic | 0.7648 | pathogenic | -0.739 | Destabilizing | 0.407 | N | 0.413 | neutral | None | None | None | None | N |
| V/Q | 0.5333 | ambiguous | 0.6252 | pathogenic | -1.759 | Destabilizing | 0.766 | D | 0.415 | neutral | None | None | None | None | N |
| V/R | 0.5694 | likely_pathogenic | 0.658 | pathogenic | -1.52 | Destabilizing | 0.908 | D | 0.445 | neutral | None | None | None | None | N |
| V/S | 0.4042 | ambiguous | 0.5091 | ambiguous | -2.528 | Highly Destabilizing | 0.636 | D | 0.378 | neutral | None | None | None | None | N |
| V/T | 0.3358 | likely_benign | 0.4157 | ambiguous | -2.113 | Highly Destabilizing | 0.09 | N | 0.241 | neutral | None | None | None | None | N |
| V/W | 0.7732 | likely_pathogenic | 0.8424 | pathogenic | -1.581 | Destabilizing | 0.99 | D | 0.577 | neutral | None | None | None | None | N |
| V/Y | 0.6009 | likely_pathogenic | 0.6825 | pathogenic | -1.136 | Destabilizing | 0.764 | D | 0.376 | 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.