Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28682 | 86269;86270;86271 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| N2AB | 27041 | 81346;81347;81348 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| N2A | 26114 | 78565;78566;78567 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| N2B | 19617 | 59074;59075;59076 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| Novex-1 | 19742 | 59449;59450;59451 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| Novex-2 | 19809 | 59650;59651;59652 | chr2:178560088;178560087;178560086 | chr2:179424815;179424814;179424813 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs760467197  |
-0.1 | 1.0 | N | 0.715 | 0.428 | 0.682346832895 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 4.48E-05 | 0 |
| P/L | rs760467197 |
-0.1 | 1.0 | N | 0.715 | 0.428 | 0.682346832895 | gnomAD-4.0.0 | 1.71063E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.00903E-04 | None | 0 | 0 | 1.8889E-05 | 0 | 0 |
| P/S | rs1158588206 |
-0.217 | 1.0 | N | 0.757 | 0.365 | 0.380730819819 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0727 | likely_benign | 0.0738 | benign | -0.462 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | N | 0.491777777 | None | None | I |
| P/C | 0.5197 | ambiguous | 0.5124 | ambiguous | -0.474 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| P/D | 0.4351 | ambiguous | 0.4531 | ambiguous | -0.368 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/E | 0.2706 | likely_benign | 0.2811 | benign | -0.495 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | I |
| P/F | 0.5163 | ambiguous | 0.5322 | ambiguous | -0.775 | Destabilizing | 1.0 | D | 0.617 | neutral | None | None | None | None | I |
| P/G | 0.3546 | ambiguous | 0.364 | ambiguous | -0.589 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| P/H | 0.2443 | likely_benign | 0.2503 | benign | -0.236 | Destabilizing | 1.0 | D | 0.643 | neutral | None | None | None | None | I |
| P/I | 0.2628 | likely_benign | 0.2603 | benign | -0.279 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/K | 0.3413 | ambiguous | 0.3428 | ambiguous | -0.379 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | I |
| P/L | 0.1171 | likely_benign | 0.1197 | benign | -0.279 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.495276845 | None | None | I |
| P/M | 0.2652 | likely_benign | 0.2672 | benign | -0.223 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | I |
| P/N | 0.2929 | likely_benign | 0.3075 | benign | -0.045 | Destabilizing | 1.0 | D | 0.712 | prob.delet. | None | None | None | None | I |
| P/Q | 0.1552 | likely_benign | 0.1546 | benign | -0.327 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | N | 0.477626663 | None | None | I |
| P/R | 0.2761 | likely_benign | 0.2694 | benign | 0.155 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.470322509 | None | None | I |
| P/S | 0.1282 | likely_benign | 0.1315 | benign | -0.383 | Destabilizing | 1.0 | D | 0.757 | deleterious | N | 0.510902255 | None | None | I |
| P/T | 0.1036 | likely_benign | 0.1059 | benign | -0.412 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | D | 0.524812915 | None | None | I |
| P/V | 0.1633 | likely_benign | 0.1622 | benign | -0.305 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| P/W | 0.7477 | likely_pathogenic | 0.7467 | pathogenic | -0.856 | Destabilizing | 1.0 | D | 0.666 | neutral | None | None | None | None | I |
| P/Y | 0.5118 | ambiguous | 0.5144 | ambiguous | -0.544 | Destabilizing | 1.0 | D | 0.63 | 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.