Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14821 | 44686;44687;44688 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| N2AB | 13180 | 39763;39764;39765 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| N2A | 12253 | 36982;36983;36984 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| N2B | 5756 | 17491;17492;17493 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| Novex-1 | 5881 | 17866;17867;17868 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| Novex-2 | 5948 | 18067;18068;18069 | chr2:178625360;178625359;178625358 | chr2:179490087;179490086;179490085 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs756640775  |
0.027 | 0.026 | N | 0.351 | 0.199 | 0.347217280506 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 1.63036E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs756640775 |
0.027 | 0.026 | N | 0.351 | 0.199 | 0.347217280506 | gnomAD-4.0.0 | 4.15124E-06 | None | None | None | None | N | None | 0 | 9.57763E-05 | None | 0 | 0 | None | 0 | 0 | 1.80923E-06 | 0 | 0 |
| T/S | None | None | 0.946 | N | 0.523 | 0.286 | 0.379707525713 | gnomAD-4.0.0 | 3.45799E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61749E-06 | 0 | 1.67364E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1799 | likely_benign | 0.1835 | benign | -1.291 | Destabilizing | 0.64 | D | 0.561 | neutral | N | 0.515317617 | None | None | N |
| T/C | 0.574 | likely_pathogenic | 0.5446 | ambiguous | -1.17 | Destabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | N |
| T/D | 0.7155 | likely_pathogenic | 0.7128 | pathogenic | -1.785 | Destabilizing | 0.996 | D | 0.698 | prob.neutral | None | None | None | None | N |
| T/E | 0.5341 | ambiguous | 0.5485 | ambiguous | -1.614 | Destabilizing | 0.988 | D | 0.663 | neutral | None | None | None | None | N |
| T/F | 0.2862 | likely_benign | 0.2916 | benign | -0.897 | Destabilizing | 0.976 | D | 0.725 | prob.delet. | None | None | None | None | N |
| T/G | 0.6031 | likely_pathogenic | 0.6025 | pathogenic | -1.671 | Destabilizing | 0.988 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/H | 0.3704 | ambiguous | 0.3782 | ambiguous | -1.731 | Destabilizing | 0.999 | D | 0.737 | prob.delet. | None | None | None | None | N |
| T/I | 0.1262 | likely_benign | 0.1189 | benign | -0.305 | Destabilizing | 0.026 | N | 0.351 | neutral | N | 0.494306145 | None | None | N |
| T/K | 0.3886 | ambiguous | 0.4088 | ambiguous | -0.929 | Destabilizing | 0.988 | D | 0.673 | neutral | None | None | None | None | N |
| T/L | 0.1221 | likely_benign | 0.1224 | benign | -0.305 | Destabilizing | 0.702 | D | 0.507 | neutral | None | None | None | None | N |
| T/M | 0.1031 | likely_benign | 0.1101 | benign | -0.367 | Destabilizing | 0.976 | D | 0.709 | prob.delet. | None | None | None | None | N |
| T/N | 0.2699 | likely_benign | 0.2773 | benign | -1.501 | Destabilizing | 0.995 | D | 0.591 | neutral | D | 0.597316637 | None | None | N |
| T/P | 0.7085 | likely_pathogenic | 0.6868 | pathogenic | -0.603 | Destabilizing | 0.995 | D | 0.701 | prob.neutral | D | 0.661181175 | None | None | N |
| T/Q | 0.3394 | likely_benign | 0.3605 | ambiguous | -1.374 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/R | 0.3106 | likely_benign | 0.3237 | benign | -0.971 | Destabilizing | 0.988 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/S | 0.2211 | likely_benign | 0.2227 | benign | -1.692 | Destabilizing | 0.946 | D | 0.523 | neutral | N | 0.517226669 | None | None | N |
| T/V | 0.1323 | likely_benign | 0.1207 | benign | -0.603 | Destabilizing | 0.034 | N | 0.284 | neutral | None | None | None | None | N |
| T/W | 0.677 | likely_pathogenic | 0.6751 | pathogenic | -1.01 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3481 | ambiguous | 0.3596 | ambiguous | -0.671 | Destabilizing | 0.988 | D | 0.747 | deleterious | 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.