Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14557 | 43894;43895;43896 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| N2AB | 12916 | 38971;38972;38973 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| N2A | 11989 | 36190;36191;36192 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| N2B | 5492 | 16699;16700;16701 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| Novex-1 | 5617 | 17074;17075;17076 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| Novex-2 | 5684 | 17275;17276;17277 | chr2:178632225;178632224;178632223 | chr2:179496952;179496951;179496950 |
| 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 | 0.22 | D | 0.499 | 0.526 | 0.477917065107 | gnomAD-4.0.0 | 1.60684E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.89408E-05 | 0 | 0 | 0 | 0 |
| D/N | rs794729431  |
None | None | N | 0.145 | 0.259 | 0.298056030225 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs794729431 |
None | None | N | 0.145 | 0.259 | 0.298056030225 | gnomAD-4.0.0 | 1.5495E-05 | None | None | None | None | N | None | 1.69474E-05 | 0 | None | 0 | 0 | None | 1.57679E-05 | 0 | 2.40981E-05 | 0 | 0 |
| D/Y | None | None | 0.859 | D | 0.579 | 0.63 | 0.474010150167 | gnomAD-4.0.0 | 1.60671E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.88203E-06 | 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 | 0.2496 | likely_benign | 0.1909 | benign | -0.41 | Destabilizing | 0.22 | N | 0.499 | neutral | D | 0.548129704 | None | None | N |
| D/C | 0.7 | likely_pathogenic | 0.6214 | pathogenic | 0.095 | Stabilizing | 0.968 | D | 0.649 | neutral | None | None | None | None | N |
| D/E | 0.25 | likely_benign | 0.1987 | benign | -0.221 | Destabilizing | 0.002 | N | 0.16 | neutral | N | 0.439687899 | None | None | N |
| D/F | 0.5785 | likely_pathogenic | 0.4836 | ambiguous | -0.378 | Destabilizing | 0.89 | D | 0.583 | neutral | None | None | None | None | N |
| D/G | 0.1574 | likely_benign | 0.1269 | benign | -0.585 | Destabilizing | 0.124 | N | 0.439 | neutral | N | 0.51950504 | None | None | N |
| D/H | 0.3081 | likely_benign | 0.2448 | benign | -0.242 | Destabilizing | 0.497 | N | 0.437 | neutral | D | 0.581434506 | None | None | N |
| D/I | 0.5169 | ambiguous | 0.4208 | ambiguous | 0.002 | Stabilizing | 0.726 | D | 0.583 | neutral | None | None | None | None | N |
| D/K | 0.4477 | ambiguous | 0.3511 | ambiguous | 0.423 | Stabilizing | 0.157 | N | 0.449 | neutral | None | None | None | None | N |
| D/L | 0.4993 | ambiguous | 0.4002 | ambiguous | 0.002 | Stabilizing | 0.567 | D | 0.544 | neutral | None | None | None | None | N |
| D/M | 0.7242 | likely_pathogenic | 0.6279 | pathogenic | 0.226 | Stabilizing | 0.968 | D | 0.575 | neutral | None | None | None | None | N |
| D/N | 0.0832 | likely_benign | 0.0703 | benign | 0.107 | Stabilizing | None | N | 0.145 | neutral | N | 0.520133874 | None | None | N |
| D/P | 0.8316 | likely_pathogenic | 0.7979 | pathogenic | -0.115 | Destabilizing | 0.726 | D | 0.444 | neutral | None | None | None | None | N |
| D/Q | 0.4448 | ambiguous | 0.3494 | ambiguous | 0.124 | Stabilizing | 0.567 | D | 0.413 | neutral | None | None | None | None | N |
| D/R | 0.4475 | ambiguous | 0.3658 | ambiguous | 0.504 | Stabilizing | 0.567 | D | 0.49 | neutral | None | None | None | None | N |
| D/S | 0.1665 | likely_benign | 0.1292 | benign | 0.01 | Stabilizing | 0.157 | N | 0.439 | neutral | None | None | None | None | N |
| D/T | 0.3667 | ambiguous | 0.2871 | benign | 0.152 | Stabilizing | 0.157 | N | 0.479 | neutral | None | None | None | None | N |
| D/V | 0.326 | likely_benign | 0.2688 | benign | -0.115 | Destabilizing | 0.667 | D | 0.545 | neutral | D | 0.580997989 | None | None | N |
| D/W | 0.8549 | likely_pathogenic | 0.8048 | pathogenic | -0.225 | Destabilizing | 0.968 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/Y | 0.1724 | likely_benign | 0.1425 | benign | -0.135 | Destabilizing | 0.859 | D | 0.579 | neutral | D | 0.580997989 | 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.