Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15170 | 45733;45734;45735 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| N2AB | 13529 | 40810;40811;40812 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| N2A | 12602 | 38029;38030;38031 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| N2B | 6105 | 18538;18539;18540 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| Novex-1 | 6230 | 18913;18914;18915 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| Novex-2 | 6297 | 19114;19115;19116 | chr2:178621210;178621209;178621208 | chr2:179485937;179485936;179485935 |
| 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/E | None | None | 0.37 | N | 0.259 | 0.105 | 0.291694819147 | gnomAD-4.0.0 | 1.36937E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99819E-07 | 0 | 1.6587E-05 |
| D/N | rs751407435  |
0.454 | 0.997 | D | 0.439 | 0.389 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| D/N | rs751407435 |
0.454 | 0.997 | D | 0.439 | 0.389 | None | gnomAD-4.0.0 | 1.30101E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61979E-05 | 0 | 1.65909E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2237 | likely_benign | 0.192 | benign | -0.103 | Destabilizing | 0.978 | D | 0.473 | neutral | D | 0.619025798 | None | None | N |
| D/C | 0.7732 | likely_pathogenic | 0.7204 | pathogenic | 0.058 | Stabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| D/E | 0.1682 | likely_benign | 0.1426 | benign | -0.269 | Destabilizing | 0.37 | N | 0.259 | neutral | N | 0.505472462 | None | None | N |
| D/F | 0.7013 | likely_pathogenic | 0.6609 | pathogenic | -0.109 | Destabilizing | 1.0 | D | 0.593 | neutral | None | None | None | None | N |
| D/G | 0.2736 | likely_benign | 0.2416 | benign | -0.276 | Destabilizing | 0.121 | N | 0.286 | neutral | D | 0.573435207 | None | None | N |
| D/H | 0.4152 | ambiguous | 0.3592 | ambiguous | 0.177 | Stabilizing | 1.0 | D | 0.527 | neutral | D | 0.679096468 | None | None | N |
| D/I | 0.4408 | ambiguous | 0.3898 | ambiguous | 0.297 | Stabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | N |
| D/K | 0.4643 | ambiguous | 0.4044 | ambiguous | 0.443 | Stabilizing | 0.995 | D | 0.47 | neutral | None | None | None | None | N |
| D/L | 0.5164 | ambiguous | 0.4659 | ambiguous | 0.297 | Stabilizing | 0.998 | D | 0.618 | neutral | None | None | None | None | N |
| D/M | 0.7196 | likely_pathogenic | 0.6679 | pathogenic | 0.303 | Stabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| D/N | 0.118 | likely_benign | 0.1082 | benign | 0.163 | Stabilizing | 0.997 | D | 0.439 | neutral | D | 0.539288192 | None | None | N |
| D/P | 0.9034 | likely_pathogenic | 0.8902 | pathogenic | 0.186 | Stabilizing | 0.999 | D | 0.533 | neutral | None | None | None | None | N |
| D/Q | 0.437 | ambiguous | 0.3738 | ambiguous | 0.184 | Stabilizing | 0.995 | D | 0.485 | neutral | None | None | None | None | N |
| D/R | 0.5535 | ambiguous | 0.4926 | ambiguous | 0.616 | Stabilizing | 0.995 | D | 0.563 | neutral | None | None | None | None | N |
| D/S | 0.1569 | likely_benign | 0.1321 | benign | 0.065 | Stabilizing | 0.983 | D | 0.418 | neutral | None | None | None | None | N |
| D/T | 0.3199 | likely_benign | 0.2723 | benign | 0.2 | Stabilizing | 0.998 | D | 0.499 | neutral | None | None | None | None | N |
| D/V | 0.2545 | likely_benign | 0.2232 | benign | 0.186 | Stabilizing | 0.997 | D | 0.629 | neutral | D | 0.664805748 | None | None | N |
| D/W | 0.9265 | likely_pathogenic | 0.9134 | pathogenic | -0.021 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| D/Y | 0.3042 | likely_benign | 0.2907 | benign | 0.126 | Stabilizing | 1.0 | D | 0.599 | neutral | D | 0.754560174 | 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.