Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26906 | 80941;80942;80943 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| N2AB | 25265 | 76018;76019;76020 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| N2A | 24338 | 73237;73238;73239 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| N2B | 17841 | 53746;53747;53748 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| Novex-1 | 17966 | 54121;54122;54123 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| Novex-2 | 18033 | 54322;54323;54324 | chr2:178565416;178565415;178565414 | chr2:179430143;179430142;179430141 |
| 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/Q | rs536183519  |
-0.009 | 1.0 | D | 0.598 | 0.369 | 0.420322003156 | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | I | None | 1.2408E-04 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 2.34E-05 | 0 |
| R/Q | rs536183519 |
-0.009 | 1.0 | D | 0.598 | 0.369 | 0.420322003156 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 2.07211E-04 | 0 |
| R/Q | rs536183519 |
-0.009 | 1.0 | D | 0.598 | 0.369 | 0.420322003156 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1E-03 | None |
| R/Q | rs536183519 |
-0.009 | 1.0 | D | 0.598 | 0.369 | 0.420322003156 | gnomAD-4.0.0 | 1.85953E-05 | None | None | None | None | I | None | 6.67254E-05 | 1.66778E-05 | None | 0 | 0 | None | 0 | 8.26173E-04 | 1.35636E-05 | 1.0988E-05 | 3.20225E-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 | 0.8785 | likely_pathogenic | 0.8921 | pathogenic | 0.136 | Stabilizing | 0.992 | D | 0.615 | neutral | None | None | None | None | I |
| R/C | 0.2651 | likely_benign | 0.3344 | benign | -0.096 | Destabilizing | 0.46 | N | 0.597 | neutral | None | None | None | None | I |
| R/D | 0.9773 | likely_pathogenic | 0.9769 | pathogenic | -0.221 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | I |
| R/E | 0.8364 | likely_pathogenic | 0.847 | pathogenic | -0.162 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | I |
| R/F | 0.7728 | likely_pathogenic | 0.8011 | pathogenic | -0.1 | Destabilizing | 1.0 | D | 0.625 | neutral | None | None | None | None | I |
| R/G | 0.8402 | likely_pathogenic | 0.8552 | pathogenic | -0.041 | Destabilizing | 0.998 | D | 0.59 | neutral | N | 0.514432555 | None | None | I |
| R/H | 0.1617 | likely_benign | 0.2122 | benign | -0.574 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | I |
| R/I | 0.4939 | ambiguous | 0.5262 | ambiguous | 0.563 | Stabilizing | 0.999 | D | 0.613 | neutral | None | None | None | None | I |
| R/K | 0.212 | likely_benign | 0.2312 | benign | -0.02 | Destabilizing | 0.999 | D | 0.539 | neutral | None | None | None | None | I |
| R/L | 0.5303 | ambiguous | 0.5682 | pathogenic | 0.563 | Stabilizing | 0.996 | D | 0.638 | neutral | N | 0.511201405 | None | None | I |
| R/M | 0.6194 | likely_pathogenic | 0.6642 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | I |
| R/N | 0.8959 | likely_pathogenic | 0.9138 | pathogenic | 0.109 | Stabilizing | 1.0 | D | 0.598 | neutral | None | None | None | None | I |
| R/P | 0.9907 | likely_pathogenic | 0.9893 | pathogenic | 0.441 | Stabilizing | 1.0 | D | 0.612 | neutral | N | 0.514686044 | None | None | I |
| R/Q | 0.2015 | likely_benign | 0.2383 | benign | 0.067 | Stabilizing | 1.0 | D | 0.598 | neutral | D | 0.52711222 | None | None | I |
| R/S | 0.8783 | likely_pathogenic | 0.8953 | pathogenic | -0.093 | Destabilizing | 0.996 | D | 0.625 | neutral | None | None | None | None | I |
| R/T | 0.7526 | likely_pathogenic | 0.7944 | pathogenic | 0.087 | Stabilizing | 0.996 | D | 0.621 | neutral | None | None | None | None | I |
| R/V | 0.6588 | likely_pathogenic | 0.6825 | pathogenic | 0.441 | Stabilizing | 0.998 | D | 0.593 | neutral | None | None | None | None | I |
| R/W | 0.3316 | likely_benign | 0.3768 | ambiguous | -0.243 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | I |
| R/Y | 0.5415 | ambiguous | 0.6032 | pathogenic | 0.17 | Stabilizing | 1.0 | D | 0.621 | neutral | 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.