Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22189 | 66790;66791;66792 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| N2AB | 20548 | 61867;61868;61869 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| N2A | 19621 | 59086;59087;59088 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| N2B | 13124 | 39595;39596;39597 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| Novex-1 | 13249 | 39970;39971;39972 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| Novex-2 | 13316 | 40171;40172;40173 | chr2:178581703;178581702;178581701 | chr2:179446430;179446429;179446428 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs369934753  |
-1.597 | 0.946 | N | 0.543 | 0.36 | None | gnomAD-2.1.1 | 1.44E-05 | None | None | None | None | I | None | 4.17E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.37E-05 | 0 |
| I/T | rs369934753 |
-1.597 | 0.946 | N | 0.543 | 0.36 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| I/T | rs369934753 |
-1.597 | 0.946 | N | 0.543 | 0.36 | None | gnomAD-4.0.0 | 3.84645E-05 | None | None | None | None | I | None | 1.33583E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08921E-05 | 0 | 1.60354E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1961 | likely_benign | 0.2053 | benign | -0.89 | Destabilizing | 0.919 | D | 0.489 | neutral | None | None | None | None | I |
| I/C | 0.728 | likely_pathogenic | 0.722 | pathogenic | -0.627 | Destabilizing | 0.999 | D | 0.601 | neutral | None | None | None | None | I |
| I/D | 0.7823 | likely_pathogenic | 0.784 | pathogenic | -0.373 | Destabilizing | 0.996 | D | 0.739 | prob.delet. | None | None | None | None | I |
| I/E | 0.5405 | ambiguous | 0.5265 | ambiguous | -0.463 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | None | None | None | None | I |
| I/F | 0.2403 | likely_benign | 0.2244 | benign | -0.852 | Destabilizing | 0.968 | D | 0.499 | neutral | D | 0.523097975 | None | None | I |
| I/G | 0.6938 | likely_pathogenic | 0.6984 | pathogenic | -1.081 | Destabilizing | 0.996 | D | 0.729 | prob.delet. | None | None | None | None | I |
| I/H | 0.5635 | ambiguous | 0.552 | ambiguous | -0.321 | Destabilizing | 0.999 | D | 0.76 | deleterious | None | None | None | None | I |
| I/K | 0.3651 | ambiguous | 0.37 | ambiguous | -0.459 | Destabilizing | 0.988 | D | 0.731 | prob.delet. | None | None | None | None | I |
| I/L | 0.0792 | likely_benign | 0.0839 | benign | -0.502 | Destabilizing | 0.011 | N | 0.137 | neutral | N | 0.385164813 | None | None | I |
| I/M | 0.0947 | likely_benign | 0.0957 | benign | -0.365 | Destabilizing | 0.968 | D | 0.517 | neutral | N | 0.500645189 | None | None | I |
| I/N | 0.3968 | ambiguous | 0.3958 | ambiguous | -0.226 | Destabilizing | 0.995 | D | 0.743 | deleterious | N | 0.477594971 | None | None | I |
| I/P | 0.8881 | likely_pathogenic | 0.9246 | pathogenic | -0.597 | Destabilizing | 0.996 | D | 0.743 | deleterious | None | None | None | None | I |
| I/Q | 0.3972 | ambiguous | 0.3986 | ambiguous | -0.499 | Destabilizing | 0.996 | D | 0.741 | deleterious | None | None | None | None | I |
| I/R | 0.2956 | likely_benign | 0.315 | benign | 0.168 | Stabilizing | 0.988 | D | 0.745 | deleterious | None | None | None | None | I |
| I/S | 0.2579 | likely_benign | 0.2594 | benign | -0.721 | Destabilizing | 0.984 | D | 0.599 | neutral | N | 0.40446265 | None | None | I |
| I/T | 0.0737 | likely_benign | 0.077 | benign | -0.703 | Destabilizing | 0.946 | D | 0.543 | neutral | N | 0.364402752 | None | None | I |
| I/V | 0.0944 | likely_benign | 0.088 | benign | -0.597 | Destabilizing | 0.437 | N | 0.329 | neutral | N | 0.469282132 | None | None | I |
| I/W | 0.7932 | likely_pathogenic | 0.7904 | pathogenic | -0.842 | Destabilizing | 0.999 | D | 0.77 | deleterious | None | None | None | None | I |
| I/Y | 0.6118 | likely_pathogenic | 0.6204 | pathogenic | -0.597 | Destabilizing | 0.996 | D | 0.622 | neutral | None | None | None | None | I |
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.