Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31130 | 93613;93614;93615 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| N2AB | 29489 | 88690;88691;88692 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| N2A | 28562 | 85909;85910;85911 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| N2B | 22065 | 66418;66419;66420 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| Novex-1 | 22190 | 66793;66794;66795 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| Novex-2 | 22257 | 66994;66995;66996 | chr2:178548238;178548237;178548236 | chr2:179412965;179412964;179412963 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.417 | N | 0.627 | 0.286 | 0.33340067248 | gnomAD-4.0.0 | 6.84182E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15931E-05 | 0 |
| A/T | rs759107930  |
-1.215 | 0.442 | N | 0.625 | 0.254 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 2.67E-05 | 0 |
| A/T | rs759107930 |
-1.215 | 0.442 | N | 0.625 | 0.254 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 9.44E-05 | 0 | 2.94E-05 | 0 | 0 |
| A/T | rs759107930 |
-1.215 | 0.442 | N | 0.625 | 0.254 | None | gnomAD-4.0.0 | 3.65627E-05 | None | None | None | None | N | None | 1.33533E-05 | 0 | None | 0 | 0 | None | 3.12559E-05 | 0 | 4.57701E-05 | 2.19592E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4832 | ambiguous | 0.4837 | ambiguous | -1.782 | Destabilizing | 0.909 | D | 0.701 | prob.neutral | None | None | None | None | N |
| A/D | 0.9914 | likely_pathogenic | 0.989 | pathogenic | -1.787 | Destabilizing | 0.726 | D | 0.81 | deleterious | None | None | None | None | N |
| A/E | 0.9794 | likely_pathogenic | 0.9719 | pathogenic | -1.586 | Destabilizing | 0.667 | D | 0.811 | deleterious | N | 0.49579337 | None | None | N |
| A/F | 0.8632 | likely_pathogenic | 0.8281 | pathogenic | -0.865 | Destabilizing | 0.567 | D | 0.799 | deleterious | None | None | None | None | N |
| A/G | 0.4767 | ambiguous | 0.445 | ambiguous | -1.675 | Destabilizing | 0.364 | N | 0.621 | neutral | N | 0.476675157 | None | None | N |
| A/H | 0.9873 | likely_pathogenic | 0.9841 | pathogenic | -1.966 | Destabilizing | 0.968 | D | 0.787 | deleterious | None | None | None | None | N |
| A/I | 0.2496 | likely_benign | 0.2371 | benign | 0.155 | Stabilizing | 0.06 | N | 0.685 | prob.neutral | None | None | None | None | N |
| A/K | 0.9925 | likely_pathogenic | 0.9895 | pathogenic | -1.197 | Destabilizing | 0.726 | D | 0.809 | deleterious | None | None | None | None | N |
| A/L | 0.3131 | likely_benign | 0.2921 | benign | 0.155 | Stabilizing | 0.072 | N | 0.669 | neutral | None | None | None | None | N |
| A/M | 0.4234 | ambiguous | 0.3984 | ambiguous | -0.372 | Destabilizing | 0.567 | D | 0.792 | deleterious | None | None | None | None | N |
| A/N | 0.9671 | likely_pathogenic | 0.9624 | pathogenic | -1.501 | Destabilizing | 0.89 | D | 0.785 | deleterious | None | None | None | None | N |
| A/P | 0.9798 | likely_pathogenic | 0.9684 | pathogenic | -0.244 | Destabilizing | 0.939 | D | 0.811 | deleterious | N | 0.49579337 | None | None | N |
| A/Q | 0.9657 | likely_pathogenic | 0.9582 | pathogenic | -1.284 | Destabilizing | 0.89 | D | 0.787 | deleterious | None | None | None | None | N |
| A/R | 0.9802 | likely_pathogenic | 0.9733 | pathogenic | -1.364 | Destabilizing | 0.726 | D | 0.803 | deleterious | None | None | None | None | N |
| A/S | 0.3321 | likely_benign | 0.3322 | benign | -2.09 | Highly Destabilizing | 0.417 | N | 0.627 | neutral | N | 0.472662685 | None | None | N |
| A/T | 0.1735 | likely_benign | 0.1771 | benign | -1.727 | Destabilizing | 0.442 | N | 0.625 | neutral | N | 0.476928646 | None | None | N |
| A/V | 0.0883 | likely_benign | 0.0814 | benign | -0.244 | Destabilizing | None | N | 0.265 | neutral | N | 0.360690443 | None | None | N |
| A/W | 0.9919 | likely_pathogenic | 0.9881 | pathogenic | -1.442 | Destabilizing | 0.968 | D | 0.787 | deleterious | None | None | None | None | N |
| A/Y | 0.9695 | likely_pathogenic | 0.9598 | pathogenic | -0.919 | Destabilizing | 0.726 | D | 0.787 | deleterious | 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.