Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24677 | 74254;74255;74256 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| N2AB | 23036 | 69331;69332;69333 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| N2A | 22109 | 66550;66551;66552 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| N2B | 15612 | 47059;47060;47061 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| Novex-1 | 15737 | 47434;47435;47436 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| Novex-2 | 15804 | 47635;47636;47637 | chr2:178572103;178572102;178572101 | chr2:179436830;179436829;179436828 |
| 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/A | rs1708422337  |
None | 0.019 | N | 0.289 | 0.157 | 0.18274738541 | 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 |
| T/A | rs1708422337 |
None | 0.019 | N | 0.289 | 0.157 | 0.18274738541 | gnomAD-4.0.0 | 6.57635E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47089E-05 | 0 | 0 |
| T/S | rs749016497 |
-0.056 | 0.419 | N | 0.441 | 0.115 | 0.173771789658 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/S | rs749016497 |
-0.056 | 0.419 | N | 0.441 | 0.115 | 0.173771789658 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07383E-04 | 0 |
| T/S | rs749016497 |
-0.056 | 0.419 | N | 0.441 | 0.115 | 0.173771789658 | gnomAD-4.0.0 | 1.23976E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.19669E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.08 | likely_benign | 0.0739 | benign | -0.469 | Destabilizing | 0.019 | N | 0.289 | neutral | N | 0.475487069 | None | None | N |
| T/C | 0.3618 | ambiguous | 0.3343 | benign | -0.269 | Destabilizing | 0.999 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/D | 0.3961 | ambiguous | 0.3524 | ambiguous | 0.281 | Stabilizing | 0.977 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/E | 0.3227 | likely_benign | 0.2808 | benign | 0.2 | Stabilizing | 0.993 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/F | 0.2779 | likely_benign | 0.2305 | benign | -1.007 | Destabilizing | 0.998 | D | 0.769 | deleterious | None | None | None | None | N |
| T/G | 0.1842 | likely_benign | 0.1673 | benign | -0.583 | Destabilizing | 0.98 | D | 0.633 | neutral | None | None | None | None | N |
| T/H | 0.2344 | likely_benign | 0.1963 | benign | -0.894 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| T/I | 0.1782 | likely_benign | 0.1514 | benign | -0.286 | Destabilizing | 0.912 | D | 0.615 | neutral | N | 0.481362872 | None | None | N |
| T/K | 0.1965 | likely_benign | 0.1477 | benign | -0.315 | Destabilizing | 0.995 | D | 0.68 | prob.neutral | None | None | None | None | N |
| T/L | 0.1038 | likely_benign | 0.09 | benign | -0.286 | Destabilizing | 0.932 | D | 0.505 | neutral | None | None | None | None | N |
| T/M | 0.0997 | likely_benign | 0.0875 | benign | -0.033 | Destabilizing | 0.999 | D | 0.708 | prob.delet. | None | None | None | None | N |
| T/N | 0.1096 | likely_benign | 0.1023 | benign | -0.101 | Destabilizing | 0.99 | D | 0.605 | neutral | N | 0.468383498 | None | None | N |
| T/P | 0.1108 | likely_benign | 0.1 | benign | -0.32 | Destabilizing | 0.969 | D | 0.729 | prob.delet. | N | 0.471194655 | None | None | N |
| T/Q | 0.2179 | likely_benign | 0.1774 | benign | -0.342 | Destabilizing | 0.996 | D | 0.728 | prob.delet. | None | None | None | None | N |
| T/R | 0.1948 | likely_benign | 0.1484 | benign | -0.061 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | N |
| T/S | 0.0878 | likely_benign | 0.0835 | benign | -0.344 | Destabilizing | 0.419 | N | 0.441 | neutral | N | 0.451160519 | None | None | N |
| T/V | 0.1338 | likely_benign | 0.1204 | benign | -0.32 | Destabilizing | 0.208 | N | 0.385 | neutral | None | None | None | None | N |
| T/W | 0.6379 | likely_pathogenic | 0.5579 | ambiguous | -0.987 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/Y | 0.311 | likely_benign | 0.2626 | benign | -0.707 | Destabilizing | 0.999 | D | 0.771 | deleterious | 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.