Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17113 | 51562;51563;51564 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| N2AB | 15472 | 46639;46640;46641 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| N2A | 14545 | 43858;43859;43860 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| N2B | 8048 | 24367;24368;24369 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| Novex-1 | 8173 | 24742;24743;24744 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| Novex-2 | 8240 | 24943;24944;24945 | chr2:178610189;178610188;178610187 | chr2:179474916;179474915;179474914 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs763635220  |
None | 0.998 | D | 0.746 | 0.54 | 0.639464360942 | gnomAD-4.0.0 | 1.5928E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86151E-06 | 0 | 0 |
| P/Q | rs763635220 |
None | 0.962 | N | 0.383 | 0.457 | 0.399304321381 | gnomAD-4.0.0 | 3.18561E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72302E-06 | 0 | 0 |
| P/S | rs768641489 |
-0.821 | 0.998 | N | 0.729 | 0.549 | 0.418221603839 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 1.78E-05 | 0 |
| P/S | rs768641489 |
-0.821 | 0.998 | N | 0.729 | 0.549 | 0.418221603839 | gnomAD-4.0.0 | 2.22991E-05 | None | None | None | None | N | None | 0 | 4.57519E-05 | None | 0 | 0 | None | 3.76492E-05 | 0 | 1.14458E-05 | 4.29947E-05 | 9.0854E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1511 | likely_benign | 0.1705 | benign | -0.727 | Destabilizing | 0.992 | D | 0.653 | neutral | N | 0.517858018 | None | None | N |
| P/C | 0.7652 | likely_pathogenic | 0.85 | pathogenic | -0.613 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| P/D | 0.8667 | likely_pathogenic | 0.8798 | pathogenic | -0.524 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| P/E | 0.5695 | likely_pathogenic | 0.6008 | pathogenic | -0.641 | Destabilizing | 0.988 | D | 0.677 | prob.neutral | None | None | None | None | N |
| P/F | 0.8392 | likely_pathogenic | 0.8984 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| P/G | 0.5886 | likely_pathogenic | 0.6424 | pathogenic | -0.88 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| P/H | 0.5552 | ambiguous | 0.6331 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| P/I | 0.5704 | likely_pathogenic | 0.6659 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| P/K | 0.7769 | likely_pathogenic | 0.8269 | pathogenic | -0.566 | Destabilizing | 0.996 | D | 0.733 | prob.delet. | None | None | None | None | N |
| P/L | 0.2941 | likely_benign | 0.3989 | ambiguous | -0.469 | Destabilizing | 0.998 | D | 0.746 | deleterious | D | 0.53069403 | None | None | N |
| P/M | 0.5756 | likely_pathogenic | 0.6735 | pathogenic | -0.335 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| P/N | 0.6762 | likely_pathogenic | 0.7227 | pathogenic | -0.254 | Destabilizing | 0.999 | D | 0.714 | prob.delet. | None | None | None | None | N |
| P/Q | 0.3547 | ambiguous | 0.4076 | ambiguous | -0.545 | Destabilizing | 0.962 | D | 0.383 | neutral | N | 0.511588194 | None | None | N |
| P/R | 0.6406 | likely_pathogenic | 0.7119 | pathogenic | 0.023 | Stabilizing | 0.998 | D | 0.725 | prob.delet. | N | 0.503142383 | None | None | N |
| P/S | 0.2957 | likely_benign | 0.3415 | ambiguous | -0.633 | Destabilizing | 0.998 | D | 0.729 | prob.delet. | N | 0.518956883 | None | None | N |
| P/T | 0.2614 | likely_benign | 0.3177 | benign | -0.65 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | N | 0.518956883 | None | None | N |
| P/V | 0.4014 | ambiguous | 0.4784 | ambiguous | -0.52 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| P/W | 0.9203 | likely_pathogenic | 0.9506 | pathogenic | -0.997 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| P/Y | 0.8393 | likely_pathogenic | 0.8962 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.775 | 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.