Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6936 | 21031;21032;21033 | chr2:178725398;178725397;178725396 | chr2:179590125;179590124;179590123 |
| N2AB | 6619 | 20080;20081;20082 | chr2:178725398;178725397;178725396 | chr2:179590125;179590124;179590123 |
| N2A | 5692 | 17299;17300;17301 | chr2:178725398;178725397;178725396 | chr2:179590125;179590124;179590123 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs1206230320  |
-0.684 | None | N | None | 0.191 | None | gnomAD-2.1.1 | 4.35E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.71E-05 | None | 0 | 0 | 0 |
| R/K | rs1206230320 |
-0.684 | None | N | None | 0.191 | None | gnomAD-4.0.0 | 2.77145E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.07604E-07 | 3.63064E-05 | 0 |
| R/W | rs762861187 |
-0.149 | None | N | None | 0.452 | None | gnomAD-2.1.1 | 1.14E-05 | None | None | None | None | I | None | 1.2727E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs762861187 |
-0.149 | None | N | None | 0.452 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs762861187 |
-0.149 | None | N | None | 0.452 | None | gnomAD-4.0.0 | 6.54822E-06 | None | None | None | None | I | None | 8.48205E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3658 | ambiguous | 0.3709 | ambiguous | -0.116 | Destabilizing | None | None | None | None | None | None | None | None | I |
| R/C | 0.2245 | likely_benign | 0.2174 | benign | -0.204 | Destabilizing | None | None | None | None | None | None | None | None | I |
| R/D | 0.743 | likely_pathogenic | 0.7548 | pathogenic | -0.032 | Destabilizing | None | None | None | None | None | None | None | None | I |
| R/E | 0.3519 | ambiguous | 0.3661 | ambiguous | 0.088 | Stabilizing | None | N | 0.083 | neutral | None | None | None | None | I |
| R/F | 0.6164 | likely_pathogenic | 0.6153 | pathogenic | -0.009 | Destabilizing | None | None | None | None | None | None | None | None | I |
| R/G | 0.3277 | likely_benign | 0.3461 | ambiguous | -0.398 | Destabilizing | None | None | None | None | N | 0.490492176 | None | None | I |
| R/H | 0.1501 | likely_benign | 0.1565 | benign | -0.935 | Destabilizing | None | None | None | None | None | None | None | None | I |
| R/I | 0.2883 | likely_benign | 0.2937 | benign | 0.621 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/K | 0.1158 | likely_benign | 0.1127 | benign | -0.155 | Destabilizing | None | None | None | None | N | 0.504408718 | None | None | I |
| R/L | 0.2892 | likely_benign | 0.3075 | benign | 0.621 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/M | 0.2781 | likely_benign | 0.2976 | benign | 0.01 | Stabilizing | None | None | None | None | N | 0.512164197 | None | None | I |
| R/N | 0.6424 | likely_pathogenic | 0.6556 | pathogenic | 0.076 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/P | 0.8843 | likely_pathogenic | 0.9206 | pathogenic | 0.398 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/Q | 0.1024 | likely_benign | 0.1035 | benign | 0.054 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/S | 0.5232 | ambiguous | 0.5339 | ambiguous | -0.343 | Destabilizing | None | None | None | None | N | 0.462388738 | None | None | I |
| R/T | 0.2642 | likely_benign | 0.2626 | benign | -0.051 | Destabilizing | None | None | None | None | N | 0.472240372 | None | None | I |
| R/V | 0.3365 | likely_benign | 0.332 | benign | 0.398 | Stabilizing | None | None | None | None | None | None | None | None | I |
| R/W | 0.2101 | likely_benign | 0.2355 | benign | 0.071 | Stabilizing | None | None | None | None | N | 0.491252645 | None | None | I |
| R/Y | 0.4578 | ambiguous | 0.4554 | ambiguous | 0.424 | Stabilizing | None | None | None | None | 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.