Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26376 | 79351;79352;79353 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| N2AB | 24735 | 74428;74429;74430 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| N2A | 23808 | 71647;71648;71649 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| N2B | 17311 | 52156;52157;52158 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| Novex-1 | 17436 | 52531;52532;52533 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| Novex-2 | 17503 | 52732;52733;52734 | chr2:178567006;178567005;178567004 | chr2:179431733;179431732;179431731 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/E | rs397517714  |
None | 0.002 | N | 0.605 | 0.21 | 0.278968121808 | 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 |
| A/E | rs397517714 |
None | 0.002 | N | 0.605 | 0.21 | 0.278968121808 | gnomAD-4.0.0 | 1.23957E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.6954E-06 | 0 | 0 |
| A/G | None | None | 0.361 | N | 0.659 | 0.032 | 0.222439326576 | gnomAD-4.0.0 | 6.8427E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99546E-07 | 0 | 0 |
| A/V | rs397517714 |
0.37 | 0.001 | N | 0.269 | 0.09 | 0.305086939656 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/V | rs397517714 |
0.37 | 0.001 | N | 0.269 | 0.09 | 0.305086939656 | gnomAD-4.0.0 | 1.16326E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52923E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3208 | likely_benign | 0.2926 | benign | -0.878 | Destabilizing | 0.984 | D | 0.667 | prob.neutral | None | None | None | None | N |
| A/D | 0.1326 | likely_benign | 0.1254 | benign | -0.56 | Destabilizing | 0.272 | N | 0.672 | prob.neutral | None | None | None | None | N |
| A/E | 0.1183 | likely_benign | 0.1131 | benign | -0.653 | Destabilizing | 0.002 | N | 0.605 | neutral | N | 0.349956161 | None | None | N |
| A/F | 0.2062 | likely_benign | 0.1801 | benign | -0.7 | Destabilizing | 0.724 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/G | 0.1126 | likely_benign | 0.1017 | benign | -0.54 | Destabilizing | 0.361 | N | 0.659 | prob.neutral | N | 0.446906705 | None | None | N |
| A/H | 0.2854 | likely_benign | 0.2613 | benign | -0.496 | Destabilizing | 0.842 | D | 0.655 | prob.neutral | None | None | None | None | N |
| A/I | 0.1154 | likely_benign | 0.0991 | benign | -0.217 | Destabilizing | 0.272 | N | 0.713 | prob.delet. | None | None | None | None | N |
| A/K | 0.2099 | likely_benign | 0.1973 | benign | -0.916 | Destabilizing | 0.002 | N | 0.592 | neutral | None | None | None | None | N |
| A/L | 0.0862 | likely_benign | 0.0793 | benign | -0.217 | Destabilizing | 0.134 | N | 0.636 | neutral | None | None | None | None | N |
| A/M | 0.1185 | likely_benign | 0.1044 | benign | -0.429 | Destabilizing | 0.063 | N | 0.635 | neutral | None | None | None | None | N |
| A/N | 0.1292 | likely_benign | 0.1138 | benign | -0.7 | Destabilizing | 0.724 | D | 0.689 | prob.delet. | None | None | None | None | N |
| A/P | 0.102 | likely_benign | 0.1016 | benign | -0.241 | Destabilizing | 0.8 | D | 0.77 | deleterious | N | 0.47532267 | None | None | N |
| A/Q | 0.175 | likely_benign | 0.159 | benign | -0.881 | Destabilizing | 0.272 | N | 0.772 | deleterious | None | None | None | None | N |
| A/R | 0.2493 | likely_benign | 0.2349 | benign | -0.489 | Destabilizing | 0.002 | N | 0.608 | neutral | None | None | None | None | N |
| A/S | 0.0758 | likely_benign | 0.0707 | benign | -0.951 | Destabilizing | 0.22 | N | 0.574 | neutral | N | 0.391514782 | None | None | N |
| A/T | 0.0653 | likely_benign | 0.0631 | benign | -0.949 | Destabilizing | 0.361 | N | 0.666 | prob.neutral | N | 0.440364735 | None | None | N |
| A/V | 0.0733 | likely_benign | 0.0655 | benign | -0.241 | Destabilizing | 0.001 | N | 0.269 | neutral | N | 0.436148207 | None | None | N |
| A/W | 0.5772 | likely_pathogenic | 0.5412 | ambiguous | -0.928 | Destabilizing | 0.984 | D | 0.707 | prob.delet. | None | None | None | None | N |
| A/Y | 0.2882 | likely_benign | 0.2636 | benign | -0.56 | Destabilizing | 0.942 | D | 0.661 | prob.neutral | 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.