Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14776 | 44551;44552;44553 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| N2AB | 13135 | 39628;39629;39630 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| N2A | 12208 | 36847;36848;36849 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| N2B | 5711 | 17356;17357;17358 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| Novex-1 | 5836 | 17731;17732;17733 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| Novex-2 | 5903 | 17932;17933;17934 | chr2:178629399;178629398;178629397 | chr2:179494126;179494125;179494124 |
| 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 | rs1250844275  |
-0.048 | 1.0 | N | 0.687 | 0.489 | 0.650954787814 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/I | rs1250844275 |
-0.048 | 1.0 | N | 0.687 | 0.489 | 0.650954787814 | gnomAD-4.0.0 | 1.3691E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79962E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1794 | likely_benign | 0.1772 | benign | -0.156 | Destabilizing | 0.999 | D | 0.602 | neutral | N | 0.509509492 | None | None | N |
| T/C | 0.7662 | likely_pathogenic | 0.7639 | pathogenic | -0.32 | Destabilizing | 1.0 | D | 0.637 | neutral | None | None | None | None | N |
| T/D | 0.7743 | likely_pathogenic | 0.7665 | pathogenic | 0.104 | Stabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/E | 0.5832 | likely_pathogenic | 0.5592 | ambiguous | 0.014 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/F | 0.4735 | ambiguous | 0.4606 | ambiguous | -0.78 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| T/G | 0.6115 | likely_pathogenic | 0.5654 | pathogenic | -0.233 | Destabilizing | 1.0 | D | 0.73 | prob.delet. | None | None | None | None | N |
| T/H | 0.6122 | likely_pathogenic | 0.6113 | pathogenic | -0.448 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/I | 0.2749 | likely_benign | 0.3004 | benign | -0.08 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.506294339 | None | None | N |
| T/K | 0.4526 | ambiguous | 0.4554 | ambiguous | -0.274 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/L | 0.161 | likely_benign | 0.1698 | benign | -0.08 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| T/M | 0.118 | likely_benign | 0.1253 | benign | -0.08 | Destabilizing | 1.0 | D | 0.641 | neutral | None | None | None | None | N |
| T/N | 0.3212 | likely_benign | 0.3391 | benign | -0.079 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | N | 0.507807706 | None | None | N |
| T/P | 0.3975 | ambiguous | 0.4008 | ambiguous | -0.08 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.511441714 | None | None | N |
| T/Q | 0.4585 | ambiguous | 0.4607 | ambiguous | -0.289 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| T/R | 0.4035 | ambiguous | 0.4032 | ambiguous | -0.005 | Destabilizing | 1.0 | D | 0.672 | neutral | None | None | None | None | N |
| T/S | 0.2898 | likely_benign | 0.2835 | benign | -0.247 | Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.488996512 | None | None | N |
| T/V | 0.2169 | likely_benign | 0.2231 | benign | -0.08 | Destabilizing | 0.999 | D | 0.661 | neutral | None | None | None | None | N |
| T/W | 0.8595 | likely_pathogenic | 0.8325 | pathogenic | -0.855 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/Y | 0.588 | likely_pathogenic | 0.5773 | pathogenic | -0.533 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | 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.