Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35951 | 108076;108077;108078 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| N2AB | 34310 | 103153;103154;103155 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| N2A | 33383 | 100372;100373;100374 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| N2B | 26886 | 80881;80882;80883 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| Novex-1 | 27011 | 81256;81257;81258 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| Novex-2 | 27078 | 81457;81458;81459 | chr2:178527137;178527136;178527135 | chr2:179391864;179391863;179391862 |
| 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/E | rs770407405  |
-0.012 | None | N | 0.118 | 0.111 | 0.0297737177859 | gnomAD-2.1.1 | 3.21E-05 | None | None | None | -0.179(OBSL1) -0.023(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 2.61438E-04 | None | 0 | 0 | 0 |
| D/E | rs770407405 |
-0.012 | None | N | 0.118 | 0.111 | 0.0297737177859 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | -0.179(OBSL1) -0.023(OBSCN) | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| D/E | rs770407405 |
-0.012 | None | N | 0.118 | 0.111 | 0.0297737177859 | gnomAD-4.0.0 | 9.91405E-06 | None | None | None | -0.179(OBSL1) -0.023(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.75674E-04 | 0 |
| D/G | rs1212826574 |
None | 0.165 | N | 0.277 | 0.175 | 0.119812018005 | gnomAD-4.0.0 | 1.36828E-06 | None | None | None | -0.343(OBSL1) -0.272(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7988E-06 | 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 | 0.1756 | likely_benign | 0.158 | benign | -0.164 | Destabilizing | 0.09 | N | 0.293 | neutral | N | 0.463078518 | None | -0.156(OBSL1) -0.095(OBSCN) | N |
| D/C | 0.7199 | likely_pathogenic | 0.6826 | pathogenic | 0.006 | Stabilizing | 0.981 | D | 0.217 | neutral | None | None | None | -0.083(OBSL1) -0.006(OBSCN) | N |
| D/E | 0.1198 | likely_benign | 0.1198 | benign | -0.264 | Destabilizing | None | N | 0.118 | neutral | N | 0.397757603 | None | -0.179(OBSL1) -0.023(OBSCN) | N |
| D/F | 0.7379 | likely_pathogenic | 0.6904 | pathogenic | -0.101 | Destabilizing | 0.932 | D | 0.227 | neutral | None | None | None | 0.076(OBSL1) 0.11(OBSCN) | N |
| D/G | 0.167 | likely_benign | 0.1488 | benign | -0.344 | Destabilizing | 0.165 | N | 0.277 | neutral | N | 0.399946972 | None | -0.343(OBSL1) -0.272(OBSCN) | N |
| D/H | 0.3362 | likely_benign | 0.2918 | benign | 0.229 | Stabilizing | 0.773 | D | 0.22 | neutral | N | 0.482184354 | None | 0.726(OBSL1) 0.669(OBSCN) | N |
| D/I | 0.5002 | ambiguous | 0.4474 | ambiguous | 0.258 | Stabilizing | 0.818 | D | 0.273 | neutral | None | None | None | 0.374(OBSL1) 0.409(OBSCN) | N |
| D/K | 0.2873 | likely_benign | 0.2587 | benign | 0.405 | Stabilizing | 0.116 | N | 0.283 | neutral | None | None | None | 0.325(OBSL1) 0.314(OBSCN) | N |
| D/L | 0.5068 | ambiguous | 0.4518 | ambiguous | 0.258 | Stabilizing | 0.388 | N | 0.302 | neutral | None | None | None | 0.374(OBSL1) 0.409(OBSCN) | N |
| D/M | 0.6958 | likely_pathogenic | 0.6484 | pathogenic | 0.258 | Stabilizing | 0.932 | D | 0.215 | neutral | None | None | None | 0.898(OBSL1) 0.931(OBSCN) | N |
| D/N | 0.1087 | likely_benign | 0.1008 | benign | 0.073 | Stabilizing | 0.324 | N | 0.239 | neutral | N | 0.460595573 | None | -1.298(OBSL1) -1.263(OBSCN) | N |
| D/P | 0.5781 | likely_pathogenic | 0.5396 | ambiguous | 0.139 | Stabilizing | 0.563 | D | 0.305 | neutral | None | None | None | 0.205(OBSL1) 0.249(OBSCN) | N |
| D/Q | 0.32 | likely_benign | 0.2876 | benign | 0.114 | Stabilizing | 0.024 | N | 0.188 | neutral | None | None | None | -0.677(OBSL1) -0.634(OBSCN) | N |
| D/R | 0.3354 | likely_benign | 0.2979 | benign | 0.615 | Stabilizing | 0.388 | N | 0.331 | neutral | None | None | None | 0.158(OBSL1) 0.102(OBSCN) | N |
| D/S | 0.1201 | likely_benign | 0.1101 | benign | -0.016 | Destabilizing | 0.024 | N | 0.15 | neutral | None | None | None | -1.011(OBSL1) -0.981(OBSCN) | N |
| D/T | 0.2778 | likely_benign | 0.248 | benign | 0.13 | Stabilizing | 0.241 | N | 0.281 | neutral | None | None | None | -0.803(OBSL1) -0.78(OBSCN) | N |
| D/V | 0.313 | likely_benign | 0.2726 | benign | 0.139 | Stabilizing | 0.324 | N | 0.333 | neutral | N | 0.508928238 | None | 0.205(OBSL1) 0.249(OBSCN) | N |
| D/W | 0.9038 | likely_pathogenic | 0.8812 | pathogenic | 0.013 | Stabilizing | 0.981 | D | 0.255 | neutral | None | None | None | -0.087(OBSL1) -0.07(OBSCN) | N |
| D/Y | 0.3525 | ambiguous | 0.3061 | benign | 0.14 | Stabilizing | 0.912 | D | 0.236 | neutral | N | 0.455833926 | None | 0.056(OBSL1) 0.073(OBSCN) | 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.