Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1580 | 4963;4964;4965 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| N2AB | 1580 | 4963;4964;4965 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| N2A | 1580 | 4963;4964;4965 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| N2B | 1534 | 4825;4826;4827 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| Novex-1 | 1534 | 4825;4826;4827 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| Novex-2 | 1534 | 4825;4826;4827 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
| Novex-3 | 1580 | 4963;4964;4965 | chr2:178777225;178777224;178777223 | chr2:179641952;179641951;179641950 |
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/M | rs73973147  |
0.231 | 0.007 | D | 0.181 | 0.149 | None | gnomAD-2.1.1 | 1.77738E-03 | None | None | None | None | I | None | 1.75066E-02 | 1.04449E-03 | None | 0 | 0 | None | 2.28654E-04 | None | 0 | 9.32E-05 | 1.24723E-03 |
| T/M | rs73973147 |
0.231 | 0.007 | D | 0.181 | 0.149 | None | gnomAD-3.1.2 | 5.1129E-03 | None | None | None | None | I | None | 1.70658E-02 | 3.07592E-03 | 0 | 0 | 0 | None | 0 | 3.16456E-03 | 2.05773E-04 | 2.07039E-04 | 3.82044E-03 |
| T/M | rs73973147 |
0.231 | 0.007 | D | 0.181 | 0.149 | None | 1000 genomes | 5.59105E-03 | None | None | None | None | I | None | 1.89E-02 | 4.3E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/M | rs73973147 |
0.231 | 0.007 | D | 0.181 | 0.149 | None | gnomAD-4.0.0 | 1.07864E-03 | None | None | None | None | I | None | 1.80342E-02 | 1.51616E-03 | None | 0 | 4.45831E-05 | None | 0 | 2.30947E-03 | 1.33901E-04 | 3.29374E-04 | 1.48776E-03 |
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 | 0.0797 | likely_benign | 0.0752 | benign | -0.721 | Destabilizing | 0.001 | N | 0.073 | neutral | N | 0.511459652 | None | None | I |
| T/C | 0.4295 | ambiguous | 0.3812 | ambiguous | -0.333 | Destabilizing | 0.859 | D | 0.279 | neutral | None | None | None | None | I |
| T/D | 0.4167 | ambiguous | 0.3602 | ambiguous | -0.272 | Destabilizing | 0.364 | N | 0.295 | neutral | None | None | None | None | I |
| T/E | 0.23 | likely_benign | 0.1994 | benign | -0.295 | Destabilizing | 0.22 | N | 0.272 | neutral | None | None | None | None | I |
| T/F | 0.17 | likely_benign | 0.1541 | benign | -0.844 | Destabilizing | 0.22 | N | 0.401 | neutral | None | None | None | None | I |
| T/G | 0.2317 | likely_benign | 0.2155 | benign | -0.961 | Destabilizing | 0.104 | N | 0.256 | neutral | None | None | None | None | I |
| T/H | 0.2324 | likely_benign | 0.2004 | benign | -1.273 | Destabilizing | 0.667 | D | 0.32 | neutral | None | None | None | None | I |
| T/I | 0.0962 | likely_benign | 0.0815 | benign | -0.179 | Destabilizing | 0.002 | N | 0.16 | neutral | None | None | None | None | I |
| T/K | 0.1359 | likely_benign | 0.1234 | benign | -0.776 | Destabilizing | 0.1 | N | 0.261 | neutral | N | 0.509489816 | None | None | I |
| T/L | 0.071 | likely_benign | 0.0673 | benign | -0.179 | Destabilizing | 0.004 | N | 0.211 | neutral | None | None | None | None | I |
| T/M | 0.0671 | likely_benign | 0.0737 | benign | 0.176 | Stabilizing | 0.007 | N | 0.181 | neutral | D | 0.588480456 | None | None | I |
| T/N | 0.1515 | likely_benign | 0.1322 | benign | -0.597 | Destabilizing | 0.22 | N | 0.219 | neutral | None | None | None | None | I |
| T/P | 0.4672 | ambiguous | 0.4648 | ambiguous | -0.328 | Destabilizing | 0.301 | N | 0.364 | neutral | D | 0.612627894 | None | None | I |
| T/Q | 0.1598 | likely_benign | 0.1423 | benign | -0.795 | Destabilizing | 0.22 | N | 0.358 | neutral | None | None | None | None | I |
| T/R | 0.1088 | likely_benign | 0.104 | benign | -0.502 | Destabilizing | 0.002 | N | 0.231 | neutral | N | 0.511490213 | None | None | I |
| T/S | 0.1076 | likely_benign | 0.1016 | benign | -0.839 | Destabilizing | 0.042 | N | 0.191 | neutral | N | 0.490346106 | None | None | I |
| T/V | 0.0804 | likely_benign | 0.073 | benign | -0.328 | Destabilizing | None | N | 0.079 | neutral | None | None | None | None | I |
| T/W | 0.4687 | ambiguous | 0.4307 | ambiguous | -0.795 | Destabilizing | 0.958 | D | 0.308 | neutral | None | None | None | None | I |
| T/Y | 0.2618 | likely_benign | 0.2397 | benign | -0.576 | Destabilizing | 0.667 | D | 0.435 | neutral | 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.