Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19336 | 58231;58232;58233 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| N2AB | 17695 | 53308;53309;53310 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| N2A | 16768 | 50527;50528;50529 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| N2B | 10271 | 31036;31037;31038 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| Novex-1 | 10396 | 31411;31412;31413 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| Novex-2 | 10463 | 31612;31613;31614 | chr2:178594488;178594487;178594486 | chr2:179459215;179459214;179459213 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | rs371851242  |
0.21 | 0.033 | N | 0.422 | 0.045 | None | gnomAD-2.1.1 | 3.21E-05 | None | None | None | None | N | None | 0 | 1.1327E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.9E-05 | 0 |
| N/I | rs371851242 |
0.21 | 0.033 | N | 0.422 | 0.045 | None | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 1.96696E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| N/I | rs371851242 |
0.21 | 0.033 | N | 0.422 | 0.045 | None | gnomAD-4.0.0 | 5.82666E-05 | None | None | None | None | N | None | 0 | 1.33462E-04 | None | 0 | 0 | None | 0 | 0 | 7.2061E-05 | 0 | 1.60128E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.0852 | likely_benign | 0.0928 | benign | -0.118 | Destabilizing | 0.004 | N | 0.168 | neutral | None | None | None | None | N |
| N/C | 0.1882 | likely_benign | 0.1893 | benign | 0.149 | Stabilizing | 0.55 | D | 0.275 | neutral | None | None | None | None | N |
| N/D | 0.0846 | likely_benign | 0.074 | benign | -0.015 | Destabilizing | None | N | 0.073 | neutral | N | 0.358981076 | None | None | N |
| N/E | 0.1404 | likely_benign | 0.1325 | benign | -0.087 | Destabilizing | None | N | 0.034 | neutral | None | None | None | None | N |
| N/F | 0.3989 | ambiguous | 0.3985 | ambiguous | -0.748 | Destabilizing | 0.245 | N | 0.366 | neutral | None | None | None | None | N |
| N/G | 0.1211 | likely_benign | 0.1311 | benign | -0.185 | Destabilizing | 0.004 | N | 0.147 | neutral | None | None | None | None | N |
| N/H | 0.0939 | likely_benign | 0.0847 | benign | -0.23 | Destabilizing | 0.196 | N | 0.241 | neutral | N | 0.443618471 | None | None | N |
| N/I | 0.1627 | likely_benign | 0.1613 | benign | -0.041 | Destabilizing | 0.033 | N | 0.422 | neutral | N | 0.425934 | None | None | N |
| N/K | 0.1179 | likely_benign | 0.0966 | benign | 0.083 | Stabilizing | None | N | 0.033 | neutral | N | 0.358250357 | None | None | N |
| N/L | 0.163 | likely_benign | 0.1623 | benign | -0.041 | Destabilizing | 0.009 | N | 0.257 | neutral | None | None | None | None | N |
| N/M | 0.2062 | likely_benign | 0.2126 | benign | 0.088 | Stabilizing | 0.245 | N | 0.273 | neutral | None | None | None | None | N |
| N/P | 0.1633 | likely_benign | 0.1733 | benign | -0.046 | Destabilizing | 0.044 | N | 0.311 | neutral | None | None | None | None | N |
| N/Q | 0.1365 | likely_benign | 0.1334 | benign | -0.234 | Destabilizing | 0.001 | N | 0.074 | neutral | None | None | None | None | N |
| N/R | 0.1593 | likely_benign | 0.1373 | benign | 0.159 | Stabilizing | 0.009 | N | 0.165 | neutral | None | None | None | None | N |
| N/S | 0.0558 | likely_benign | 0.0588 | benign | -0.007 | Destabilizing | None | N | 0.073 | neutral | N | 0.409793899 | None | None | N |
| N/T | 0.0658 | likely_benign | 0.0702 | benign | 0.019 | Stabilizing | None | N | 0.068 | neutral | N | 0.39401637 | None | None | N |
| N/V | 0.1345 | likely_benign | 0.1392 | benign | -0.046 | Destabilizing | 0.009 | N | 0.255 | neutral | None | None | None | None | N |
| N/W | 0.5528 | ambiguous | 0.5356 | ambiguous | -0.894 | Destabilizing | 0.788 | D | 0.295 | neutral | None | None | None | None | N |
| N/Y | 0.1632 | likely_benign | 0.1505 | benign | -0.573 | Destabilizing | 0.196 | N | 0.357 | neutral | N | 0.443618471 | 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.