Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25939 | 78040;78041;78042 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| N2AB | 24298 | 73117;73118;73119 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| N2A | 23371 | 70336;70337;70338 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| N2B | 16874 | 50845;50846;50847 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| Novex-1 | 16999 | 51220;51221;51222 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| Novex-2 | 17066 | 51421;51422;51423 | chr2:178568317;178568316;178568315 | chr2:179433044;179433043;179433042 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | rs397517712  |
-0.358 | 0.005 | N | 0.284 | 0.116 | 0.244539031024 | gnomAD-2.1.1 | 2.14E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.91E-05 | 1.40726E-04 |
| D/A | rs397517712 |
-0.358 | 0.005 | N | 0.284 | 0.116 | 0.244539031024 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| D/A | rs397517712 |
-0.358 | 0.005 | N | 0.284 | 0.116 | 0.244539031024 | gnomAD-4.0.0 | 4.71075E-05 | None | None | None | None | N | None | 1.33572E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.18836E-05 | 0 | 3.20328E-05 |
| D/E | None | None | None | N | 0.092 | 0.124 | 0.0297737177859 | gnomAD-4.0.0 | 6.84336E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99573E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.152 | likely_benign | 0.1588 | benign | -0.51 | Destabilizing | 0.005 | N | 0.284 | neutral | N | 0.393226936 | None | None | N |
| D/C | 0.5553 | ambiguous | 0.5493 | ambiguous | -0.316 | Destabilizing | 0.864 | D | 0.293 | neutral | None | None | None | None | N |
| D/E | 0.0922 | likely_benign | 0.0878 | benign | -0.483 | Destabilizing | None | N | 0.092 | neutral | N | 0.362848101 | None | None | N |
| D/F | 0.598 | likely_pathogenic | 0.6336 | pathogenic | -0.006 | Destabilizing | 0.214 | N | 0.359 | neutral | None | None | None | None | N |
| D/G | 0.1924 | likely_benign | 0.2046 | benign | -0.816 | Destabilizing | 0.024 | N | 0.273 | neutral | N | 0.42306984 | None | None | N |
| D/H | 0.246 | likely_benign | 0.2417 | benign | -0.019 | Destabilizing | 0.295 | N | 0.305 | neutral | N | 0.362848101 | None | None | N |
| D/I | 0.2899 | likely_benign | 0.3146 | benign | 0.287 | Stabilizing | 0.016 | N | 0.273 | neutral | None | None | None | None | N |
| D/K | 0.3798 | ambiguous | 0.3746 | ambiguous | -0.183 | Destabilizing | 0.016 | N | 0.271 | neutral | None | None | None | None | N |
| D/L | 0.352 | ambiguous | 0.3512 | ambiguous | 0.287 | Stabilizing | 0.016 | N | 0.305 | neutral | None | None | None | None | N |
| D/M | 0.4429 | ambiguous | 0.4304 | ambiguous | 0.463 | Stabilizing | 0.007 | N | 0.283 | neutral | None | None | None | None | N |
| D/N | 0.0929 | likely_benign | 0.0975 | benign | -0.683 | Destabilizing | 0.055 | N | 0.178 | neutral | N | 0.39549645 | None | None | N |
| D/P | 0.9327 | likely_pathogenic | 0.9551 | pathogenic | 0.046 | Stabilizing | 0.136 | N | 0.311 | neutral | None | None | None | None | N |
| D/Q | 0.2584 | likely_benign | 0.2369 | benign | -0.576 | Destabilizing | 0.038 | N | 0.161 | neutral | None | None | None | None | N |
| D/R | 0.4751 | ambiguous | 0.4656 | ambiguous | 0.135 | Stabilizing | 0.038 | N | 0.315 | neutral | None | None | None | None | N |
| D/S | 0.1171 | likely_benign | 0.1165 | benign | -0.865 | Destabilizing | 0.016 | N | 0.191 | neutral | None | None | None | None | N |
| D/T | 0.1666 | likely_benign | 0.1726 | benign | -0.615 | Destabilizing | None | N | 0.186 | neutral | None | None | None | None | N |
| D/V | 0.1617 | likely_benign | 0.1717 | benign | 0.046 | Stabilizing | None | N | 0.219 | neutral | N | 0.338373731 | None | None | N |
| D/W | 0.8876 | likely_pathogenic | 0.8929 | pathogenic | 0.239 | Stabilizing | 0.864 | D | 0.311 | neutral | None | None | None | None | N |
| D/Y | 0.256 | likely_benign | 0.2803 | benign | 0.249 | Stabilizing | 0.56 | D | 0.345 | neutral | N | 0.404484079 | 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.