Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28443 | 85552;85553;85554 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| N2AB | 26802 | 80629;80630;80631 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| N2A | 25875 | 77848;77849;77850 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| N2B | 19378 | 58357;58358;58359 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| Novex-1 | 19503 | 58732;58733;58734 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| Novex-2 | 19570 | 58933;58934;58935 | chr2:178560805;178560804;178560803 | chr2:179425532;179425531;179425530 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/D | rs1703365236  |
None | 0.781 | D | 0.819 | 0.673 | 0.87943456633 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/D | rs1703365236 |
None | 0.781 | D | 0.819 | 0.673 | 0.87943456633 | gnomAD-4.0.0 | 3.84416E-06 | None | None | None | None | I | None | 1.69142E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 5.69055E-05 |
| V/I | rs762332684 |
-0.27 | 0.004 | N | 0.24 | 0.134 | None | gnomAD-2.1.1 | 5.72E-05 | None | None | None | None | I | None | 0 | 1.41635E-04 | None | 0 | 1.03082E-04 | None | 6.54E-05 | None | 0 | 4.69E-05 | 1.41004E-04 |
| V/I | rs762332684 |
-0.27 | 0.004 | N | 0.24 | 0.134 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs762332684 |
-0.27 | 0.004 | N | 0.24 | 0.134 | None | gnomAD-4.0.0 | 3.09875E-05 | None | None | None | None | I | None | 1.33461E-05 | 8.33695E-05 | None | 0 | 2.23264E-05 | None | 0 | 0 | 3.56007E-05 | 1.09794E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.5932 | likely_pathogenic | 0.5301 | ambiguous | -2.106 | Highly Destabilizing | 0.334 | N | 0.504 | neutral | N | 0.485208576 | None | None | I |
| V/C | 0.8645 | likely_pathogenic | 0.8298 | pathogenic | -1.83 | Destabilizing | 0.982 | D | 0.735 | prob.delet. | None | None | None | None | I |
| V/D | 0.9856 | likely_pathogenic | 0.9686 | pathogenic | -2.705 | Highly Destabilizing | 0.781 | D | 0.819 | deleterious | D | 0.531174592 | None | None | I |
| V/E | 0.9655 | likely_pathogenic | 0.9407 | pathogenic | -2.45 | Highly Destabilizing | 0.826 | D | 0.763 | deleterious | None | None | None | None | I |
| V/F | 0.4049 | ambiguous | 0.3253 | benign | -1.244 | Destabilizing | 0.817 | D | 0.752 | deleterious | D | 0.535811848 | None | None | I |
| V/G | 0.7869 | likely_pathogenic | 0.7007 | pathogenic | -2.698 | Highly Destabilizing | 0.781 | D | 0.787 | deleterious | N | 0.49899178 | None | None | I |
| V/H | 0.9807 | likely_pathogenic | 0.9653 | pathogenic | -2.478 | Highly Destabilizing | 0.982 | D | 0.786 | deleterious | None | None | None | None | I |
| V/I | 0.0826 | likely_benign | 0.0753 | benign | -0.434 | Destabilizing | 0.004 | N | 0.24 | neutral | N | 0.437186436 | None | None | I |
| V/K | 0.9594 | likely_pathogenic | 0.9358 | pathogenic | -1.762 | Destabilizing | 0.826 | D | 0.769 | deleterious | None | None | None | None | I |
| V/L | 0.3007 | likely_benign | 0.2735 | benign | -0.434 | Destabilizing | 0.083 | N | 0.469 | neutral | D | 0.528459014 | None | None | I |
| V/M | 0.3113 | likely_benign | 0.2553 | benign | -0.592 | Destabilizing | 0.7 | D | 0.654 | neutral | None | None | None | None | I |
| V/N | 0.9449 | likely_pathogenic | 0.8999 | pathogenic | -2.169 | Highly Destabilizing | 0.935 | D | 0.817 | deleterious | None | None | None | None | I |
| V/P | 0.9776 | likely_pathogenic | 0.9649 | pathogenic | -0.965 | Destabilizing | 0.935 | D | 0.793 | deleterious | None | None | None | None | I |
| V/Q | 0.9463 | likely_pathogenic | 0.9131 | pathogenic | -1.949 | Destabilizing | 0.935 | D | 0.787 | deleterious | None | None | None | None | I |
| V/R | 0.9285 | likely_pathogenic | 0.8912 | pathogenic | -1.705 | Destabilizing | 0.826 | D | 0.816 | deleterious | None | None | None | None | I |
| V/S | 0.8444 | likely_pathogenic | 0.7675 | pathogenic | -2.835 | Highly Destabilizing | 0.826 | D | 0.756 | deleterious | None | None | None | None | I |
| V/T | 0.7434 | likely_pathogenic | 0.6677 | pathogenic | -2.411 | Highly Destabilizing | 0.399 | N | 0.635 | neutral | None | None | None | None | I |
| V/W | 0.9718 | likely_pathogenic | 0.9492 | pathogenic | -1.752 | Destabilizing | 0.982 | D | 0.75 | deleterious | None | None | None | None | I |
| V/Y | 0.9062 | likely_pathogenic | 0.8541 | pathogenic | -1.359 | Destabilizing | 0.826 | D | 0.764 | deleterious | 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.