Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24875 | 74848;74849;74850 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| N2AB | 23234 | 69925;69926;69927 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| N2A | 22307 | 67144;67145;67146 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| N2B | 15810 | 47653;47654;47655 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| Novex-1 | 15935 | 48028;48029;48030 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| Novex-2 | 16002 | 48229;48230;48231 | chr2:178571509;178571508;178571507 | chr2:179436236;179436235;179436234 |
| 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 | rs770565202  |
-0.651 | 0.919 | N | 0.453 | 0.214 | 0.276898752692 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| T/A | rs770565202 |
-0.651 | 0.919 | N | 0.453 | 0.214 | 0.276898752692 | gnomAD-4.0.0 | 7.96194E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.42976E-05 | 0 | 0 |
| T/S | rs536979672 |
-0.574 | 0.958 | N | 0.485 | 0.223 | 0.305086939656 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.95E-06 | 0 |
| T/S | rs536979672 |
-0.574 | 0.958 | N | 0.485 | 0.223 | 0.305086939656 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs536979672 |
-0.574 | 0.958 | N | 0.485 | 0.223 | 0.305086939656 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/S | rs536979672 |
-0.574 | 0.958 | N | 0.485 | 0.223 | 0.305086939656 | gnomAD-4.0.0 | 2.56352E-06 | None | None | None | None | N | None | 1.68833E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.34041E-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 | 0.132 | likely_benign | 0.1126 | benign | -0.494 | Destabilizing | 0.919 | D | 0.453 | neutral | N | 0.450907016 | None | None | N |
| T/C | 0.6917 | likely_pathogenic | 0.6265 | pathogenic | -0.203 | Destabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | N |
| T/D | 0.6274 | likely_pathogenic | 0.5825 | pathogenic | -0.247 | Destabilizing | 0.991 | D | 0.621 | neutral | None | None | None | None | N |
| T/E | 0.3928 | ambiguous | 0.3606 | ambiguous | -0.328 | Destabilizing | 0.938 | D | 0.576 | neutral | None | None | None | None | N |
| T/F | 0.5893 | likely_pathogenic | 0.5109 | ambiguous | -0.956 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| T/G | 0.4612 | ambiguous | 0.4216 | ambiguous | -0.633 | Destabilizing | 0.991 | D | 0.615 | neutral | None | None | None | None | N |
| T/H | 0.475 | ambiguous | 0.4195 | ambiguous | -0.975 | Destabilizing | 0.999 | D | 0.648 | neutral | None | None | None | None | N |
| T/I | 0.3718 | ambiguous | 0.3005 | benign | -0.241 | Destabilizing | 0.994 | D | 0.623 | neutral | N | 0.508360596 | None | None | N |
| T/K | 0.2849 | likely_benign | 0.2626 | benign | -0.511 | Destabilizing | 0.18 | N | 0.291 | neutral | None | None | None | None | N |
| T/L | 0.1819 | likely_benign | 0.1511 | benign | -0.241 | Destabilizing | 0.968 | D | 0.58 | neutral | None | None | None | None | N |
| T/M | 0.1212 | likely_benign | 0.1069 | benign | 0.15 | Stabilizing | 1.0 | D | 0.601 | neutral | None | None | None | None | N |
| T/N | 0.2156 | likely_benign | 0.1897 | benign | -0.26 | Destabilizing | 0.988 | D | 0.658 | neutral | N | 0.450563086 | None | None | N |
| T/P | 0.1487 | likely_benign | 0.1218 | benign | -0.297 | Destabilizing | 0.994 | D | 0.627 | neutral | N | 0.389633978 | None | None | N |
| T/Q | 0.2895 | likely_benign | 0.2686 | benign | -0.574 | Destabilizing | 0.991 | D | 0.619 | neutral | None | None | None | None | N |
| T/R | 0.2856 | likely_benign | 0.2483 | benign | -0.146 | Destabilizing | 0.982 | D | 0.619 | neutral | None | None | None | None | N |
| T/S | 0.2138 | likely_benign | 0.191 | benign | -0.439 | Destabilizing | 0.958 | D | 0.485 | neutral | N | 0.487561249 | None | None | N |
| T/V | 0.2512 | likely_benign | 0.2061 | benign | -0.297 | Destabilizing | 0.968 | D | 0.584 | neutral | None | None | None | None | N |
| T/W | 0.8309 | likely_pathogenic | 0.7914 | pathogenic | -0.925 | Destabilizing | 1.0 | D | 0.696 | prob.neutral | None | None | None | None | N |
| T/Y | 0.5366 | ambiguous | 0.483 | ambiguous | -0.67 | Destabilizing | 0.998 | D | 0.675 | prob.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.