Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30214 | 90865;90866;90867 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| N2AB | 28573 | 85942;85943;85944 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| N2A | 27646 | 83161;83162;83163 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| N2B | 21149 | 63670;63671;63672 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| Novex-1 | 21274 | 64045;64046;64047 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| Novex-2 | 21341 | 64246;64247;64248 | chr2:178552260;178552259;178552258 | chr2:179416987;179416986;179416985 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | rs769553778  |
None | None | N | 0.097 | 0.041 | 0.0716867268079 | gnomAD-4.0.0 | 6.84368E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16034E-05 | 0 |
| A/T | rs769553778 |
-0.708 | None | N | 0.086 | 0.044 | 0.0762999501168 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| A/T | rs769553778 |
-0.708 | None | N | 0.086 | 0.044 | 0.0762999501168 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99612E-07 | 1.16034E-05 | 0 |
| A/V | rs1476886786 |
0.174 | None | N | 0.139 | 0.123 | 0.29527378943 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| A/V | rs1476886786 |
0.174 | None | N | 0.139 | 0.123 | 0.29527378943 | gnomAD-4.0.0 | 2.05317E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69893E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4082 | ambiguous | 0.3794 | ambiguous | -0.76 | Destabilizing | 0.245 | N | 0.435 | neutral | None | None | None | None | I |
| A/D | 0.392 | ambiguous | 0.3521 | ambiguous | -1.031 | Destabilizing | 0.009 | N | 0.412 | neutral | None | None | None | None | I |
| A/E | 0.3565 | ambiguous | 0.3184 | benign | -1.079 | Destabilizing | 0.007 | N | 0.383 | neutral | N | 0.345941916 | None | None | I |
| A/F | 0.404 | ambiguous | 0.3466 | ambiguous | -0.77 | Destabilizing | None | N | 0.246 | neutral | None | None | None | None | I |
| A/G | 0.175 | likely_benign | 0.158 | benign | -0.828 | Destabilizing | 0.007 | N | 0.28 | neutral | N | 0.480277412 | None | None | I |
| A/H | 0.5264 | ambiguous | 0.4889 | ambiguous | -0.97 | Destabilizing | 0.138 | N | 0.491 | neutral | None | None | None | None | I |
| A/I | 0.2556 | likely_benign | 0.2428 | benign | -0.224 | Destabilizing | 0.003 | N | 0.348 | neutral | None | None | None | None | I |
| A/K | 0.6429 | likely_pathogenic | 0.5893 | pathogenic | -1.195 | Destabilizing | 0.009 | N | 0.385 | neutral | None | None | None | None | I |
| A/L | 0.2184 | likely_benign | 0.1937 | benign | -0.224 | Destabilizing | 0.004 | N | 0.224 | neutral | None | None | None | None | I |
| A/M | 0.2359 | likely_benign | 0.2343 | benign | -0.294 | Destabilizing | 0.138 | N | 0.444 | neutral | None | None | None | None | I |
| A/N | 0.2726 | likely_benign | 0.2421 | benign | -0.951 | Destabilizing | 0.022 | N | 0.447 | neutral | None | None | None | None | I |
| A/P | 0.3134 | likely_benign | 0.293 | benign | -0.316 | Destabilizing | 0.033 | N | 0.443 | neutral | N | 0.480450771 | None | None | I |
| A/Q | 0.4414 | ambiguous | 0.4124 | ambiguous | -1.107 | Destabilizing | 0.044 | N | 0.503 | neutral | None | None | None | None | I |
| A/R | 0.6258 | likely_pathogenic | 0.5719 | pathogenic | -0.79 | Destabilizing | 0.044 | N | 0.445 | neutral | None | None | None | None | I |
| A/S | 0.0868 | likely_benign | 0.0799 | benign | -1.194 | Destabilizing | None | N | 0.097 | neutral | N | 0.339917234 | None | None | I |
| A/T | 0.0813 | likely_benign | 0.084 | benign | -1.156 | Destabilizing | None | N | 0.086 | neutral | N | 0.359852576 | None | None | I |
| A/V | 0.1441 | likely_benign | 0.143 | benign | -0.316 | Destabilizing | None | N | 0.139 | neutral | N | 0.431195386 | None | None | I |
| A/W | 0.8064 | likely_pathogenic | 0.762 | pathogenic | -1.119 | Destabilizing | 0.497 | N | 0.473 | neutral | None | None | None | None | I |
| A/Y | 0.5193 | ambiguous | 0.4635 | ambiguous | -0.716 | Destabilizing | None | N | 0.227 | 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.