Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22490 | 67693;67694;67695 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| N2AB | 20849 | 62770;62771;62772 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| N2A | 19922 | 59989;59990;59991 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| N2B | 13425 | 40498;40499;40500 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| Novex-1 | 13550 | 40873;40874;40875 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| Novex-2 | 13617 | 41074;41075;41076 | chr2:178579729;178579728;178579727 | chr2:179444456;179444455;179444454 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/I | rs924529776  |
-0.786 | None | N | 0.102 | 0.246 | 0.253205268125 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| F/I | rs924529776 |
-0.786 | None | N | 0.102 | 0.246 | 0.253205268125 | 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 |
| F/I | rs924529776 |
-0.786 | None | N | 0.102 | 0.246 | 0.253205268125 | gnomAD-4.0.0 | 6.57722E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47102E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.517 | ambiguous | 0.4248 | ambiguous | -1.995 | Destabilizing | 0.036 | N | 0.494 | neutral | None | None | None | None | N |
| F/C | 0.2176 | likely_benign | 0.1775 | benign | -0.829 | Destabilizing | 0.873 | D | 0.616 | neutral | N | 0.451851165 | None | None | N |
| F/D | 0.9041 | likely_pathogenic | 0.853 | pathogenic | -2.144 | Highly Destabilizing | 0.296 | N | 0.624 | neutral | None | None | None | None | N |
| F/E | 0.8401 | likely_pathogenic | 0.7862 | pathogenic | -1.935 | Destabilizing | 0.08 | N | 0.556 | neutral | None | None | None | None | N |
| F/G | 0.788 | likely_pathogenic | 0.7115 | pathogenic | -2.427 | Highly Destabilizing | 0.26 | N | 0.554 | neutral | None | None | None | None | N |
| F/H | 0.4507 | ambiguous | 0.387 | ambiguous | -1.102 | Destabilizing | 0.001 | N | 0.283 | neutral | None | None | None | None | N |
| F/I | 0.1413 | likely_benign | 0.1152 | benign | -0.614 | Destabilizing | None | N | 0.102 | neutral | N | 0.404329364 | None | None | N |
| F/K | 0.6907 | likely_pathogenic | 0.6223 | pathogenic | -1.186 | Destabilizing | 0.002 | N | 0.479 | neutral | None | None | None | None | N |
| F/L | 0.6984 | likely_pathogenic | 0.6377 | pathogenic | -0.614 | Destabilizing | None | N | 0.095 | neutral | N | 0.412543415 | None | None | N |
| F/M | 0.3201 | likely_benign | 0.2779 | benign | -0.317 | Destabilizing | 0.296 | N | 0.563 | neutral | None | None | None | None | N |
| F/N | 0.6996 | likely_pathogenic | 0.6257 | pathogenic | -1.663 | Destabilizing | 0.296 | N | 0.625 | neutral | None | None | None | None | N |
| F/P | 0.9979 | likely_pathogenic | 0.9969 | pathogenic | -1.081 | Destabilizing | 0.722 | D | 0.643 | neutral | None | None | None | None | N |
| F/Q | 0.6476 | likely_pathogenic | 0.5649 | pathogenic | -1.552 | Destabilizing | 0.016 | N | 0.487 | neutral | None | None | None | None | N |
| F/R | 0.5665 | likely_pathogenic | 0.5064 | ambiguous | -0.942 | Destabilizing | 0.08 | N | 0.599 | neutral | None | None | None | None | N |
| F/S | 0.4391 | ambiguous | 0.3575 | ambiguous | -2.276 | Highly Destabilizing | 0.116 | N | 0.512 | neutral | N | 0.423608558 | None | None | N |
| F/T | 0.4537 | ambiguous | 0.3788 | ambiguous | -1.957 | Destabilizing | 0.148 | N | 0.516 | neutral | None | None | None | None | N |
| F/V | 0.1379 | likely_benign | 0.1139 | benign | -1.081 | Destabilizing | None | N | 0.23 | neutral | N | 0.384260736 | None | None | N |
| F/W | 0.5169 | ambiguous | 0.4837 | ambiguous | 0.158 | Stabilizing | 0.901 | D | 0.558 | neutral | None | None | None | None | N |
| F/Y | 0.1222 | likely_benign | 0.1123 | benign | -0.108 | Destabilizing | 0.116 | N | 0.469 | neutral | N | 0.379868063 | 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.