Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2212 | 6859;6860;6861 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| N2AB | 2212 | 6859;6860;6861 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| N2A | 2212 | 6859;6860;6861 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| N2B | 2166 | 6721;6722;6723 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| Novex-1 | 2166 | 6721;6722;6723 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| Novex-2 | 2166 | 6721;6722;6723 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
| Novex-3 | 2212 | 6859;6860;6861 | chr2:178775077;178775076;178775075 | chr2:179639804;179639803;179639802 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs2092055359  |
None | None | N | 0.223 | 0.116 | 0.533227312814 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92234E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs2092055359 |
None | None | N | 0.223 | 0.116 | 0.533227312814 | gnomAD-4.0.0 | 6.57039E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.92234E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs771623139 |
0.325 | None | N | 0.157 | 0.125 | 0.130388298395 | gnomAD-2.1.1 | 1.19E-05 | None | None | None | None | N | None | 6.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.76E-05 | 0 |
| M/V | rs771623139 |
0.325 | None | N | 0.157 | 0.125 | 0.130388298395 | gnomAD-4.0.0 | 7.95391E-06 | None | None | None | None | N | None | 5.65547E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14273E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.144 | likely_benign | 0.1419 | benign | -0.399 | Destabilizing | None | N | 0.205 | neutral | None | None | None | None | N |
| M/C | 0.4151 | ambiguous | 0.4015 | ambiguous | -0.534 | Destabilizing | 0.132 | N | 0.272 | neutral | None | None | None | None | N |
| M/D | 0.2905 | likely_benign | 0.2827 | benign | 0.41 | Stabilizing | None | N | 0.216 | neutral | None | None | None | None | N |
| M/E | 0.1488 | likely_benign | 0.145 | benign | 0.371 | Stabilizing | 0.002 | N | 0.357 | neutral | None | None | None | None | N |
| M/F | 0.122 | likely_benign | 0.1197 | benign | 0.003 | Stabilizing | 0.009 | N | 0.259 | neutral | None | None | None | None | N |
| M/G | 0.2748 | likely_benign | 0.2671 | benign | -0.578 | Destabilizing | None | N | 0.214 | neutral | None | None | None | None | N |
| M/H | 0.172 | likely_benign | 0.1652 | benign | 0.287 | Stabilizing | 0.132 | N | 0.368 | neutral | None | None | None | None | N |
| M/I | 0.0806 | likely_benign | 0.0784 | benign | -0.021 | Destabilizing | None | N | 0.165 | neutral | N | 0.414562666 | None | None | N |
| M/K | 0.0736 | likely_benign | 0.0738 | benign | 0.388 | Stabilizing | 0.001 | N | 0.368 | neutral | N | 0.388471246 | None | None | N |
| M/L | 0.0837 | likely_benign | 0.0823 | benign | -0.021 | Destabilizing | None | N | 0.191 | neutral | N | 0.437029029 | None | None | N |
| M/N | 0.12 | likely_benign | 0.1177 | benign | 0.451 | Stabilizing | 0.009 | N | 0.357 | neutral | None | None | None | None | N |
| M/P | 0.7148 | likely_pathogenic | 0.7214 | pathogenic | -0.118 | Destabilizing | 0.018 | N | 0.432 | neutral | None | None | None | None | N |
| M/Q | 0.1036 | likely_benign | 0.101 | benign | 0.328 | Stabilizing | None | N | 0.195 | neutral | None | None | None | None | N |
| M/R | 0.075 | likely_benign | 0.0758 | benign | 0.863 | Stabilizing | 0.007 | N | 0.427 | neutral | N | 0.409413464 | None | None | N |
| M/S | 0.1382 | likely_benign | 0.135 | benign | -0.018 | Destabilizing | 0.001 | N | 0.322 | neutral | None | None | None | None | N |
| M/T | 0.0891 | likely_benign | 0.0882 | benign | 0.048 | Stabilizing | None | N | 0.223 | neutral | N | 0.400791952 | None | None | N |
| M/V | 0.0597 | likely_benign | 0.0592 | benign | -0.118 | Destabilizing | None | N | 0.157 | neutral | N | 0.337386491 | None | None | N |
| M/W | 0.3248 | likely_benign | 0.3191 | benign | -0.001 | Destabilizing | 0.316 | N | 0.281 | neutral | None | None | None | None | N |
| M/Y | 0.2594 | likely_benign | 0.2571 | benign | 0.151 | Stabilizing | 0.041 | N | 0.437 | neutral | 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.