Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14900 | 44923;44924;44925 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| N2AB | 13259 | 40000;40001;40002 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| N2A | 12332 | 37219;37220;37221 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| N2B | 5835 | 17728;17729;17730 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| Novex-1 | 5960 | 18103;18104;18105 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| Novex-2 | 6027 | 18304;18305;18306 | chr2:178624582;178624581;178624580 | chr2:179489309;179489308;179489307 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs1458633272  |
-1.384 | 0.81 | N | 0.542 | 0.439 | 0.722383096883 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/F | rs1458633272 |
-1.384 | 0.81 | N | 0.542 | 0.439 | 0.722383096883 | gnomAD-4.0.0 | 6.84613E-07 | None | None | None | None | N | None | 0 | 2.23934E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1237236347 |
-2.204 | 0.549 | D | 0.528 | 0.385 | 0.72688737328 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.12246E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1237236347 |
-2.204 | 0.549 | D | 0.528 | 0.385 | 0.72688737328 | gnomAD-4.0.0 | 3.18693E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.56545E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | None | None | 0.099 | N | 0.355 | 0.157 | 0.56977568999 | gnomAD-4.0.0 | 1.36923E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99871E-07 | 0 | 1.65821E-05 |
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 | 0.5616 | ambiguous | 0.443 | ambiguous | -2.143 | Highly Destabilizing | 0.617 | D | 0.499 | neutral | None | None | None | None | N |
| I/C | 0.9033 | likely_pathogenic | 0.8677 | pathogenic | -1.276 | Destabilizing | 0.992 | D | 0.573 | neutral | None | None | None | None | N |
| I/D | 0.8461 | likely_pathogenic | 0.8564 | pathogenic | -2.057 | Highly Destabilizing | 0.739 | D | 0.613 | neutral | None | None | None | None | N |
| I/E | 0.7479 | likely_pathogenic | 0.7463 | pathogenic | -1.933 | Destabilizing | 0.85 | D | 0.612 | neutral | None | None | None | None | N |
| I/F | 0.243 | likely_benign | 0.1823 | benign | -1.311 | Destabilizing | 0.81 | D | 0.542 | neutral | N | 0.515523136 | None | None | N |
| I/G | 0.8834 | likely_pathogenic | 0.8475 | pathogenic | -2.589 | Highly Destabilizing | 0.447 | N | 0.582 | neutral | None | None | None | None | N |
| I/H | 0.8027 | likely_pathogenic | 0.7578 | pathogenic | -1.841 | Destabilizing | 0.955 | D | 0.636 | neutral | None | None | None | None | N |
| I/K | 0.7041 | likely_pathogenic | 0.6941 | pathogenic | -1.665 | Destabilizing | 0.739 | D | 0.605 | neutral | None | None | None | None | N |
| I/L | 0.2388 | likely_benign | 0.1856 | benign | -0.912 | Destabilizing | 0.099 | N | 0.304 | neutral | N | 0.509162563 | None | None | N |
| I/M | 0.1084 | likely_benign | 0.079 | benign | -0.697 | Destabilizing | 0.045 | N | 0.294 | neutral | N | 0.50283256 | None | None | N |
| I/N | 0.4924 | ambiguous | 0.495 | ambiguous | -1.71 | Destabilizing | 0.009 | N | 0.408 | neutral | D | 0.690782863 | None | None | N |
| I/P | 0.8955 | likely_pathogenic | 0.8525 | pathogenic | -1.297 | Destabilizing | 0.92 | D | 0.641 | neutral | None | None | None | None | N |
| I/Q | 0.7221 | likely_pathogenic | 0.6902 | pathogenic | -1.738 | Destabilizing | 0.85 | D | 0.641 | neutral | None | None | None | None | N |
| I/R | 0.6284 | likely_pathogenic | 0.5997 | pathogenic | -1.173 | Destabilizing | 0.85 | D | 0.637 | neutral | None | None | None | None | N |
| I/S | 0.5524 | ambiguous | 0.4971 | ambiguous | -2.351 | Highly Destabilizing | 0.379 | N | 0.551 | neutral | D | 0.61128102 | None | None | N |
| I/T | 0.3074 | likely_benign | 0.2284 | benign | -2.097 | Highly Destabilizing | 0.549 | D | 0.528 | neutral | D | 0.552830312 | None | None | N |
| I/V | 0.1696 | likely_benign | 0.1353 | benign | -1.297 | Destabilizing | 0.099 | N | 0.355 | neutral | N | 0.494939089 | None | None | N |
| I/W | 0.8526 | likely_pathogenic | 0.8107 | pathogenic | -1.565 | Destabilizing | 0.992 | D | 0.665 | neutral | None | None | None | None | N |
| I/Y | 0.6154 | likely_pathogenic | 0.5833 | pathogenic | -1.296 | Destabilizing | 0.972 | D | 0.593 | 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.