Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20367 | 61324;61325;61326 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| N2AB | 18726 | 56401;56402;56403 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| N2A | 17799 | 53620;53621;53622 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| N2B | 11302 | 34129;34130;34131 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| Novex-1 | 11427 | 34504;34505;34506 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| Novex-2 | 11494 | 34705;34706;34707 | chr2:178590626;178590625;178590624 | chr2:179455353;179455352;179455351 |
| 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 | rs141973925  |
0.198 | 1.0 | N | 0.793 | 0.31 | None | gnomAD-2.1.1 | 3.37647E-03 | None | None | None | None | I | None | 8.27198E-04 | 1.24766E-03 | None | 1.06589E-03 | 0 | None | 4.91256E-04 | None | 1.92308E-03 | 6.12666E-03 | 3.2367E-03 |
| R/Q | rs141973925 |
0.198 | 1.0 | N | 0.793 | 0.31 | None | gnomAD-3.1.2 | 2.91536E-03 | None | None | None | None | I | None | 6.76296E-04 | 2.22951E-03 | 0 | 1.15207E-03 | 0 | None | 1.70068E-03 | 0 | 5.20849E-03 | 0 | 2.39006E-03 |
| R/Q | rs141973925 |
0.198 | 1.0 | N | 0.793 | 0.31 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 8E-04 | 2.9E-03 | None | None | 0 | 3E-03 | None | None | None | 0 | None |
| R/Q | rs141973925 |
0.198 | 1.0 | N | 0.793 | 0.31 | None | gnomAD-4.0.0 | 4.50992E-03 | None | None | None | None | I | None | 8.00512E-04 | 1.70153E-03 | None | 8.79448E-04 | 0 | None | 1.84525E-03 | 1.82119E-03 | 5.67181E-03 | 3.29786E-04 | 3.81068E-03 |
| R/W | rs727504479 |
-0.408 | 1.0 | N | 0.857 | 0.322 | None | gnomAD-2.1.1 | 6.08E-05 | None | None | None | None | I | None | 2.89495E-04 | 5.67E-05 | None | 0 | 0 | None | 0 | None | 0 | 6.26E-05 | 0 |
| R/W | rs727504479 |
-0.408 | 1.0 | N | 0.857 | 0.322 | None | gnomAD-3.1.2 | 7.24E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.17727E-04 | 0 | 0 |
| R/W | rs727504479 |
-0.408 | 1.0 | N | 0.857 | 0.322 | None | gnomAD-4.0.0 | 4.21621E-05 | None | None | None | None | I | None | 1.33604E-04 | 3.33801E-05 | None | 0 | 2.23264E-05 | None | 0 | 0 | 4.23965E-05 | 2.19829E-05 | 4.80538E-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 | 0.6496 | likely_pathogenic | 0.8531 | pathogenic | 0.144 | Stabilizing | 0.998 | D | 0.628 | neutral | None | None | None | None | I |
| R/C | 0.2656 | likely_benign | 0.4983 | ambiguous | -0.025 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | I |
| R/D | 0.8234 | likely_pathogenic | 0.9279 | pathogenic | -0.236 | Destabilizing | 0.999 | D | 0.783 | deleterious | None | None | None | None | I |
| R/E | 0.6203 | likely_pathogenic | 0.8135 | pathogenic | -0.186 | Destabilizing | 0.998 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/F | 0.7354 | likely_pathogenic | 0.8926 | pathogenic | -0.107 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| R/G | 0.487 | ambiguous | 0.7742 | pathogenic | -0.019 | Destabilizing | 1.0 | D | 0.66 | prob.neutral | N | 0.437313282 | None | None | I |
| R/H | 0.152 | likely_benign | 0.2736 | benign | -0.58 | Destabilizing | 0.999 | D | 0.829 | deleterious | None | None | None | None | I |
| R/I | 0.5398 | ambiguous | 0.7541 | pathogenic | 0.534 | Stabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | I |
| R/K | 0.1695 | likely_benign | 0.2434 | benign | 0.029 | Stabilizing | 0.995 | D | 0.635 | neutral | None | None | None | None | I |
| R/L | 0.3922 | ambiguous | 0.6309 | pathogenic | 0.534 | Stabilizing | 1.0 | D | 0.66 | prob.neutral | N | 0.453261382 | None | None | I |
| R/M | 0.537 | ambiguous | 0.7742 | pathogenic | 0.049 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| R/N | 0.7471 | likely_pathogenic | 0.8863 | pathogenic | 0.207 | Stabilizing | 0.999 | D | 0.793 | deleterious | None | None | None | None | I |
| R/P | 0.5957 | likely_pathogenic | 0.8136 | pathogenic | 0.423 | Stabilizing | 1.0 | D | 0.764 | deleterious | N | 0.463459733 | None | None | I |
| R/Q | 0.1632 | likely_benign | 0.2995 | benign | 0.148 | Stabilizing | 1.0 | D | 0.793 | deleterious | N | 0.482045494 | None | None | I |
| R/S | 0.6801 | likely_pathogenic | 0.8694 | pathogenic | 0.023 | Stabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | I |
| R/T | 0.5137 | ambiguous | 0.7804 | pathogenic | 0.186 | Stabilizing | 0.999 | D | 0.764 | deleterious | None | None | None | None | I |
| R/V | 0.5958 | likely_pathogenic | 0.804 | pathogenic | 0.423 | Stabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | I |
| R/W | 0.3052 | likely_benign | 0.5541 | ambiguous | -0.264 | Destabilizing | 1.0 | D | 0.857 | deleterious | N | 0.45677807 | None | None | I |
| R/Y | 0.5752 | likely_pathogenic | 0.7843 | pathogenic | 0.142 | Stabilizing | 0.999 | D | 0.817 | deleterious | 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.