Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2518 | 7777;7778;7779 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| N2AB | 2518 | 7777;7778;7779 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| N2A | 2518 | 7777;7778;7779 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| N2B | 2472 | 7639;7640;7641 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| Novex-1 | 2472 | 7639;7640;7641 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| Novex-2 | 2472 | 7639;7640;7641 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
| Novex-3 | 2518 | 7777;7778;7779 | chr2:178773504;178773503;178773502 | chr2:179638231;179638230;179638229 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/K | None | None | 0.014 | N | 0.493 | 0.222 | 0.646115140387 | gnomAD-4.0.0 | 6.84105E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99319E-07 | 0 | 0 |
| I/T | rs1319910280  |
-2.098 | 0.003 | N | 0.333 | 0.184 | 0.594367484798 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1319910280 |
-2.098 | 0.003 | N | 0.333 | 0.184 | 0.594367484798 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.54E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs1319910280 |
-2.098 | 0.003 | N | 0.333 | 0.184 | 0.594367484798 | gnomAD-4.0.0 | 2.47837E-06 | None | None | None | None | N | None | 0 | 3.33389E-05 | None | 0 | 0 | None | 0 | 0 | 1.69495E-06 | 0 | 0 |
| I/V | rs2091831608 |
None | None | N | 0.127 | 0.104 | 0.40146981186 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1361 | likely_benign | 0.1268 | benign | -2.419 | Highly Destabilizing | None | N | 0.199 | neutral | None | None | None | None | N |
| I/C | 0.409 | ambiguous | 0.3838 | ambiguous | -1.724 | Destabilizing | 0.245 | N | 0.456 | neutral | None | None | None | None | N |
| I/D | 0.5244 | ambiguous | 0.4983 | ambiguous | -2.504 | Highly Destabilizing | 0.085 | N | 0.564 | neutral | None | None | None | None | N |
| I/E | 0.3201 | likely_benign | 0.2983 | benign | -2.313 | Highly Destabilizing | 0.018 | N | 0.513 | neutral | None | None | None | None | N |
| I/F | 0.1158 | likely_benign | 0.1107 | benign | -1.421 | Destabilizing | 0.022 | N | 0.494 | neutral | None | None | None | None | N |
| I/G | 0.4335 | ambiguous | 0.4034 | ambiguous | -2.929 | Highly Destabilizing | 0.009 | N | 0.476 | neutral | None | None | None | None | N |
| I/H | 0.2237 | likely_benign | 0.206 | benign | -2.323 | Highly Destabilizing | 0.497 | N | 0.521 | neutral | None | None | None | None | N |
| I/K | 0.1581 | likely_benign | 0.1493 | benign | -1.889 | Destabilizing | 0.014 | N | 0.493 | neutral | N | 0.461443726 | None | None | N |
| I/L | 0.0757 | likely_benign | 0.072 | benign | -0.968 | Destabilizing | None | N | 0.141 | neutral | N | 0.502104086 | None | None | N |
| I/M | 0.0541 | likely_benign | 0.0517 | benign | -0.94 | Destabilizing | None | N | 0.137 | neutral | N | 0.452956886 | None | None | N |
| I/N | 0.1699 | likely_benign | 0.1617 | benign | -2.114 | Highly Destabilizing | 0.085 | N | 0.566 | neutral | None | None | None | None | N |
| I/P | 0.899 | likely_pathogenic | 0.8936 | pathogenic | -1.43 | Destabilizing | 0.085 | N | 0.565 | neutral | None | None | None | None | N |
| I/Q | 0.1555 | likely_benign | 0.1414 | benign | -2.03 | Highly Destabilizing | 0.044 | N | 0.564 | neutral | None | None | None | None | N |
| I/R | 0.1153 | likely_benign | 0.1081 | benign | -1.534 | Destabilizing | 0.033 | N | 0.564 | neutral | N | 0.472620702 | None | None | N |
| I/S | 0.1375 | likely_benign | 0.1285 | benign | -2.815 | Highly Destabilizing | 0.009 | N | 0.451 | neutral | None | None | None | None | N |
| I/T | 0.0806 | likely_benign | 0.0781 | benign | -2.487 | Highly Destabilizing | 0.003 | N | 0.333 | neutral | N | 0.480715989 | None | None | N |
| I/V | 0.0636 | likely_benign | 0.062 | benign | -1.43 | Destabilizing | None | N | 0.127 | neutral | N | 0.405162421 | None | None | N |
| I/W | 0.4978 | ambiguous | 0.4807 | ambiguous | -1.767 | Destabilizing | 0.788 | D | 0.525 | neutral | None | None | None | None | N |
| I/Y | 0.3418 | ambiguous | 0.3227 | benign | -1.484 | Destabilizing | 0.085 | N | 0.515 | 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.