Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28662 | 86209;86210;86211 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| N2AB | 27021 | 81286;81287;81288 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| N2A | 26094 | 78505;78506;78507 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| N2B | 19597 | 59014;59015;59016 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| Novex-1 | 19722 | 59389;59390;59391 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| Novex-2 | 19789 | 59590;59591;59592 | chr2:178560148;178560147;178560146 | chr2:179424875;179424874;179424873 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | None | None | 1.0 | N | 0.717 | 0.491 | 0.491660673884 | gnomAD-4.0.0 | 1.59154E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 0 |
| D/H | None | None | 1.0 | N | 0.639 | 0.423 | 0.405700215632 | 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 |
| D/V | rs1703115388  |
None | 1.0 | N | 0.749 | 0.573 | 0.694480664743 | gnomAD-4.0.0 | 1.59154E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85894E-06 | 0 | 0 |
| D/Y | None | None | 1.0 | N | 0.672 | 0.399 | 0.689839040572 | 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 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.7054 | likely_pathogenic | 0.5503 | ambiguous | -0.377 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.518345516 | None | None | N |
| D/C | 0.9544 | likely_pathogenic | 0.9183 | pathogenic | 0.14 | Stabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| D/E | 0.633 | likely_pathogenic | 0.4974 | ambiguous | -0.477 | Destabilizing | 1.0 | D | 0.377 | neutral | N | 0.484443586 | None | None | N |
| D/F | 0.9295 | likely_pathogenic | 0.8703 | pathogenic | -0.493 | Destabilizing | 1.0 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/G | 0.6272 | likely_pathogenic | 0.4888 | ambiguous | -0.588 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.473027853 | None | None | N |
| D/H | 0.7852 | likely_pathogenic | 0.7026 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.500730894 | None | None | N |
| D/I | 0.9361 | likely_pathogenic | 0.8736 | pathogenic | 0.137 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| D/K | 0.9356 | likely_pathogenic | 0.8882 | pathogenic | 0.255 | Stabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| D/L | 0.8994 | likely_pathogenic | 0.8249 | pathogenic | 0.137 | Stabilizing | 1.0 | D | 0.746 | deleterious | None | None | None | None | N |
| D/M | 0.9676 | likely_pathogenic | 0.939 | pathogenic | 0.49 | Stabilizing | 1.0 | D | 0.664 | neutral | None | None | None | None | N |
| D/N | 0.3006 | likely_benign | 0.2496 | benign | 0.016 | Stabilizing | 1.0 | D | 0.63 | neutral | N | 0.485137019 | None | None | N |
| D/P | 0.9943 | likely_pathogenic | 0.9917 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| D/Q | 0.8807 | likely_pathogenic | 0.8101 | pathogenic | 0.019 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| D/R | 0.9174 | likely_pathogenic | 0.8684 | pathogenic | 0.247 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | N |
| D/S | 0.4272 | ambiguous | 0.3265 | benign | -0.113 | Destabilizing | 1.0 | D | 0.668 | neutral | None | None | None | None | N |
| D/T | 0.7839 | likely_pathogenic | 0.6698 | pathogenic | 0.051 | Stabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| D/V | 0.8467 | likely_pathogenic | 0.7378 | pathogenic | -0.012 | Destabilizing | 1.0 | D | 0.749 | deleterious | N | 0.490246735 | None | None | N |
| D/W | 0.9892 | likely_pathogenic | 0.9832 | pathogenic | -0.399 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | N |
| D/Y | 0.7029 | likely_pathogenic | 0.582 | pathogenic | -0.258 | Destabilizing | 1.0 | D | 0.672 | neutral | N | 0.489374589 | 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.