Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30765 | 92518;92519;92520 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| N2AB | 29124 | 87595;87596;87597 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| N2A | 28197 | 84814;84815;84816 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| N2B | 21700 | 65323;65324;65325 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| Novex-1 | 21825 | 65698;65699;65700 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| Novex-2 | 21892 | 65899;65900;65901 | chr2:178549333;178549332;178549331 | chr2:179414060;179414059;179414058 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | None | None | 0.997 | N | 0.445 | 0.311 | 0.315903272564 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| R/K | rs373099440  |
0.028 | 0.928 | N | 0.51 | 0.183 | 0.363158594168 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/K | rs373099440 |
0.028 | 0.928 | N | 0.51 | 0.183 | 0.363158594168 | gnomAD-4.0.0 | 1.36836E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99437E-07 | 1.15934E-05 | 0 |
| R/T | rs373099440 |
0.046 | 0.969 | D | 0.451 | 0.294 | None | gnomAD-2.1.1 | 1.31908E-04 | None | None | None | None | N | None | 1.447E-03 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40135E-04 |
| R/T | rs373099440 |
0.046 | 0.969 | D | 0.451 | 0.294 | None | gnomAD-3.1.2 | 5.71624E-04 | None | None | None | None | N | None | 1.9291E-03 | 4.58475E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs373099440 |
0.046 | 0.969 | D | 0.451 | 0.294 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/T | rs373099440 |
0.046 | 0.969 | D | 0.451 | 0.294 | None | gnomAD-4.0.0 | 8.92235E-05 | None | None | None | None | N | None | 1.71876E-03 | 2.16631E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20082E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7471 | likely_pathogenic | 0.6679 | pathogenic | 0.013 | Stabilizing | 0.953 | D | 0.485 | neutral | None | None | None | None | N |
| R/C | 0.3604 | ambiguous | 0.3146 | benign | -0.308 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | N |
| R/D | 0.9243 | likely_pathogenic | 0.891 | pathogenic | -0.148 | Destabilizing | 0.998 | D | 0.551 | neutral | None | None | None | None | N |
| R/E | 0.7884 | likely_pathogenic | 0.7155 | pathogenic | -0.091 | Destabilizing | 0.992 | D | 0.449 | neutral | None | None | None | None | N |
| R/F | 0.8229 | likely_pathogenic | 0.7864 | pathogenic | -0.284 | Destabilizing | 0.986 | D | 0.615 | neutral | None | None | None | None | N |
| R/G | 0.5793 | likely_pathogenic | 0.5079 | ambiguous | -0.151 | Destabilizing | 0.997 | D | 0.445 | neutral | N | 0.513187625 | None | None | N |
| R/H | 0.1861 | likely_benign | 0.1752 | benign | -0.629 | Destabilizing | 0.999 | D | 0.477 | neutral | None | None | None | None | N |
| R/I | 0.6503 | likely_pathogenic | 0.5511 | ambiguous | 0.403 | Stabilizing | 0.964 | D | 0.545 | neutral | N | 0.488752251 | None | None | N |
| R/K | 0.2123 | likely_benign | 0.1752 | benign | -0.14 | Destabilizing | 0.928 | D | 0.51 | neutral | N | 0.486502456 | None | None | N |
| R/L | 0.5519 | ambiguous | 0.4623 | ambiguous | 0.403 | Stabilizing | 0.06 | N | 0.401 | neutral | None | None | None | None | N |
| R/M | 0.6798 | likely_pathogenic | 0.581 | pathogenic | -0.078 | Destabilizing | 0.986 | D | 0.497 | neutral | None | None | None | None | N |
| R/N | 0.8331 | likely_pathogenic | 0.7823 | pathogenic | -0.078 | Destabilizing | 0.998 | D | 0.482 | neutral | None | None | None | None | N |
| R/P | 0.9473 | likely_pathogenic | 0.9185 | pathogenic | 0.293 | Stabilizing | 0.998 | D | 0.54 | neutral | None | None | None | None | N |
| R/Q | 0.21 | likely_benign | 0.1825 | benign | -0.111 | Destabilizing | 0.998 | D | 0.493 | neutral | None | None | None | None | N |
| R/S | 0.8049 | likely_pathogenic | 0.7479 | pathogenic | -0.342 | Destabilizing | 0.991 | D | 0.449 | neutral | N | 0.462717823 | None | None | N |
| R/T | 0.6811 | likely_pathogenic | 0.5851 | pathogenic | -0.16 | Destabilizing | 0.969 | D | 0.451 | neutral | D | 0.52221254 | None | None | N |
| R/V | 0.6911 | likely_pathogenic | 0.6087 | pathogenic | 0.293 | Stabilizing | 0.91 | D | 0.52 | neutral | None | None | None | None | N |
| R/W | 0.4073 | ambiguous | 0.3677 | ambiguous | -0.425 | Destabilizing | 0.999 | D | 0.675 | prob.neutral | None | None | None | None | N |
| R/Y | 0.6276 | likely_pathogenic | 0.5773 | pathogenic | -0.003 | Destabilizing | 0.993 | D | 0.555 | 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.