Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33155 | 99688;99689;99690 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| N2AB | 31514 | 94765;94766;94767 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| N2A | 30587 | 91984;91985;91986 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| N2B | 24090 | 72493;72494;72495 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| Novex-1 | 24215 | 72868;72869;72870 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| Novex-2 | 24282 | 73069;73070;73071 | chr2:178537744;178537743;178537742 | chr2:179402471;179402470;179402469 |
| 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 | rs1692258849  |
None | 0.525 | N | 0.497 | 0.258 | 0.290590437066 | gnomAD-4.0.0 | 3.18264E-06 | None | None | None | None | N | None | 5.65739E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43275E-05 | 0 |
| T/I | rs1179270927 |
0.564 | 0.996 | N | 0.682 | 0.273 | 0.467247493403 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| T/I | rs1179270927 |
0.564 | 0.996 | N | 0.682 | 0.273 | 0.467247493403 | gnomAD-4.0.0 | 2.05265E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.5194E-05 | None | 0 | 0 | 1.79895E-06 | 0 | 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 | 0.1028 | likely_benign | 0.1255 | benign | -0.366 | Destabilizing | 0.525 | D | 0.497 | neutral | N | 0.467546628 | None | None | N |
| T/C | 0.3569 | ambiguous | 0.4497 | ambiguous | -0.364 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| T/D | 0.4089 | ambiguous | 0.4967 | ambiguous | -1.438 | Destabilizing | 0.846 | D | 0.575 | neutral | None | None | None | None | N |
| T/E | 0.383 | ambiguous | 0.4426 | ambiguous | -1.448 | Destabilizing | 0.973 | D | 0.587 | neutral | None | None | None | None | N |
| T/F | 0.2092 | likely_benign | 0.2754 | benign | -0.774 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/G | 0.2957 | likely_benign | 0.3584 | ambiguous | -0.582 | Destabilizing | 0.979 | D | 0.595 | neutral | None | None | None | None | N |
| T/H | 0.2121 | likely_benign | 0.2908 | benign | -1.073 | Destabilizing | 0.997 | D | 0.705 | prob.neutral | None | None | None | None | N |
| T/I | 0.1371 | likely_benign | 0.1591 | benign | 0.111 | Stabilizing | 0.996 | D | 0.682 | prob.neutral | N | 0.497733462 | None | None | N |
| T/K | 0.3357 | likely_benign | 0.3726 | ambiguous | -0.593 | Destabilizing | 0.975 | D | 0.606 | neutral | N | 0.510758688 | None | None | N |
| T/L | 0.1036 | likely_benign | 0.1159 | benign | 0.111 | Stabilizing | 0.99 | D | 0.602 | neutral | None | None | None | None | N |
| T/M | 0.0884 | likely_benign | 0.104 | benign | 0.607 | Stabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| T/N | 0.066 | likely_benign | 0.0842 | benign | -0.812 | Destabilizing | 0.014 | N | 0.198 | neutral | None | None | None | None | N |
| T/P | 0.7763 | likely_pathogenic | 0.787 | pathogenic | -0.018 | Destabilizing | 0.994 | D | 0.682 | prob.neutral | N | 0.490367272 | None | None | N |
| T/Q | 0.2441 | likely_benign | 0.2987 | benign | -1.117 | Destabilizing | 0.994 | D | 0.682 | prob.neutral | None | None | None | None | N |
| T/R | 0.2885 | likely_benign | 0.3342 | benign | -0.267 | Destabilizing | 0.997 | D | 0.645 | neutral | N | 0.47735819 | None | None | N |
| T/S | 0.0987 | likely_benign | 0.1185 | benign | -0.8 | Destabilizing | 0.357 | N | 0.505 | neutral | N | 0.48193729 | None | None | N |
| T/V | 0.1291 | likely_benign | 0.1433 | benign | -0.018 | Destabilizing | 0.987 | D | 0.551 | neutral | None | None | None | None | N |
| T/W | 0.5823 | likely_pathogenic | 0.6845 | pathogenic | -0.857 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/Y | 0.2211 | likely_benign | 0.2811 | benign | -0.491 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | 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.