Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23477 | 70654;70655;70656 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| N2AB | 21836 | 65731;65732;65733 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| N2A | 20909 | 62950;62951;62952 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| N2B | 14412 | 43459;43460;43461 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| Novex-1 | 14537 | 43834;43835;43836 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| Novex-2 | 14604 | 44035;44036;44037 | chr2:178575703;178575702;178575701 | chr2:179440430;179440429;179440428 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | None | None | 0.822 | N | 0.511 | 0.28 | 0.353548585375 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| A/T | rs763988813  |
-1.129 | 0.698 | N | 0.533 | 0.096 | 0.241078983079 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.6342E-04 | None | 0 | 0 | 0 |
| A/T | rs763988813 |
-1.129 | 0.698 | N | 0.533 | 0.096 | 0.241078983079 | gnomAD-4.0.0 | 8.21163E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79911E-06 | 1.15945E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6269 | likely_pathogenic | 0.6518 | pathogenic | -0.651 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | N |
| A/D | 0.8314 | likely_pathogenic | 0.8174 | pathogenic | -0.907 | Destabilizing | 0.956 | D | 0.568 | neutral | None | None | None | None | N |
| A/E | 0.7277 | likely_pathogenic | 0.7084 | pathogenic | -0.908 | Destabilizing | 0.822 | D | 0.511 | neutral | N | 0.485867738 | None | None | N |
| A/F | 0.6471 | likely_pathogenic | 0.6599 | pathogenic | -0.793 | Destabilizing | 0.956 | D | 0.629 | neutral | None | None | None | None | N |
| A/G | 0.2223 | likely_benign | 0.2317 | benign | -1.082 | Destabilizing | 0.698 | D | 0.525 | neutral | N | 0.493527216 | None | None | N |
| A/H | 0.8451 | likely_pathogenic | 0.8397 | pathogenic | -1.196 | Destabilizing | 0.998 | D | 0.637 | neutral | None | None | None | None | N |
| A/I | 0.3704 | ambiguous | 0.3687 | ambiguous | -0.171 | Destabilizing | 0.754 | D | 0.54 | neutral | None | None | None | None | N |
| A/K | 0.8578 | likely_pathogenic | 0.8283 | pathogenic | -1.044 | Destabilizing | 0.86 | D | 0.514 | neutral | None | None | None | None | N |
| A/L | 0.3702 | ambiguous | 0.3716 | ambiguous | -0.171 | Destabilizing | 0.754 | D | 0.507 | neutral | None | None | None | None | N |
| A/M | 0.3354 | likely_benign | 0.3534 | ambiguous | -0.146 | Destabilizing | 0.994 | D | 0.585 | neutral | None | None | None | None | N |
| A/N | 0.5524 | ambiguous | 0.5597 | ambiguous | -0.782 | Destabilizing | 0.956 | D | 0.593 | neutral | None | None | None | None | N |
| A/P | 0.7878 | likely_pathogenic | 0.739 | pathogenic | -0.338 | Destabilizing | 0.97 | D | 0.567 | neutral | N | 0.495778087 | None | None | N |
| A/Q | 0.7133 | likely_pathogenic | 0.6926 | pathogenic | -0.888 | Destabilizing | 0.978 | D | 0.579 | neutral | None | None | None | None | N |
| A/R | 0.8468 | likely_pathogenic | 0.8156 | pathogenic | -0.741 | Destabilizing | 0.956 | D | 0.581 | neutral | None | None | None | None | N |
| A/S | 0.1091 | likely_benign | 0.116 | benign | -1.173 | Destabilizing | 0.025 | N | 0.236 | neutral | N | 0.430361172 | None | None | N |
| A/T | 0.1183 | likely_benign | 0.132 | benign | -1.075 | Destabilizing | 0.698 | D | 0.533 | neutral | N | 0.448330857 | None | None | N |
| A/V | 0.1805 | likely_benign | 0.18 | benign | -0.338 | Destabilizing | 0.014 | N | 0.295 | neutral | N | 0.485963739 | None | None | N |
| A/W | 0.9423 | likely_pathogenic | 0.9362 | pathogenic | -1.192 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| A/Y | 0.7668 | likely_pathogenic | 0.7787 | pathogenic | -0.752 | Destabilizing | 0.978 | D | 0.641 | 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.