Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27261 | 82006;82007;82008 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| N2AB | 25620 | 77083;77084;77085 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| N2A | 24693 | 74302;74303;74304 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| N2B | 18196 | 54811;54812;54813 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| Novex-1 | 18321 | 55186;55187;55188 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| Novex-2 | 18388 | 55387;55388;55389 | chr2:178564351;178564350;178564349 | chr2:179429078;179429077;179429076 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.011 | N | 0.309 | 0.157 | 0.124217242631 | gnomAD-4.0.0 | 1.59146E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8584E-06 | 0 | 0 |
| S/T | rs1704859697  |
None | None | N | 0.076 | 0.136 | 0.0986583533028 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs1704859697 |
None | None | N | 0.076 | 0.136 | 0.0986583533028 | gnomAD-4.0.0 | 2.56249E-06 | None | None | None | None | I | None | 3.38306E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.21 | likely_benign | 0.1658 | benign | -0.841 | Destabilizing | 0.003 | N | 0.312 | neutral | None | None | None | None | I |
| S/C | 0.196 | likely_benign | 0.1727 | benign | -0.667 | Destabilizing | 0.162 | N | 0.413 | neutral | N | 0.491217332 | None | None | I |
| S/D | 0.9516 | likely_pathogenic | 0.9376 | pathogenic | -0.646 | Destabilizing | 0.035 | N | 0.28 | neutral | None | None | None | None | I |
| S/E | 0.9796 | likely_pathogenic | 0.973 | pathogenic | -0.566 | Destabilizing | 0.035 | N | 0.305 | neutral | None | None | None | None | I |
| S/F | 0.8941 | likely_pathogenic | 0.8406 | pathogenic | -0.778 | Destabilizing | 0.112 | N | 0.528 | neutral | None | None | None | None | I |
| S/G | 0.3292 | likely_benign | 0.2784 | benign | -1.17 | Destabilizing | 0.011 | N | 0.309 | neutral | N | 0.490710353 | None | None | I |
| S/H | 0.9485 | likely_pathogenic | 0.9365 | pathogenic | -1.527 | Destabilizing | 0.439 | N | 0.411 | neutral | None | None | None | None | I |
| S/I | 0.6302 | likely_pathogenic | 0.5544 | ambiguous | -0.051 | Destabilizing | 0.006 | N | 0.364 | neutral | N | 0.462055805 | None | None | I |
| S/K | 0.9924 | likely_pathogenic | 0.9898 | pathogenic | -0.608 | Destabilizing | 0.035 | N | 0.299 | neutral | None | None | None | None | I |
| S/L | 0.3537 | ambiguous | 0.2838 | benign | -0.051 | Destabilizing | 0.007 | N | 0.353 | neutral | None | None | None | None | I |
| S/M | 0.4826 | ambiguous | 0.4217 | ambiguous | 0.054 | Stabilizing | 0.204 | N | 0.423 | neutral | None | None | None | None | I |
| S/N | 0.7668 | likely_pathogenic | 0.718 | pathogenic | -0.84 | Destabilizing | 0.026 | N | 0.35 | neutral | N | 0.502320148 | None | None | I |
| S/P | 0.8902 | likely_pathogenic | 0.8508 | pathogenic | -0.279 | Destabilizing | 0.068 | N | 0.519 | neutral | None | None | None | None | I |
| S/Q | 0.969 | likely_pathogenic | 0.9623 | pathogenic | -0.856 | Destabilizing | 0.204 | N | 0.343 | neutral | None | None | None | None | I |
| S/R | 0.9878 | likely_pathogenic | 0.9841 | pathogenic | -0.652 | Destabilizing | 0.026 | N | 0.528 | neutral | N | 0.513334058 | None | None | I |
| S/T | 0.038 | likely_benign | 0.0428 | benign | -0.756 | Destabilizing | None | N | 0.076 | neutral | N | 0.427144721 | None | None | I |
| S/V | 0.441 | ambiguous | 0.3847 | ambiguous | -0.279 | Destabilizing | None | N | 0.223 | neutral | None | None | None | None | I |
| S/W | 0.9564 | likely_pathogenic | 0.9357 | pathogenic | -0.806 | Destabilizing | 0.747 | D | 0.402 | neutral | None | None | None | None | I |
| S/Y | 0.907 | likely_pathogenic | 0.867 | pathogenic | -0.49 | Destabilizing | 0.204 | N | 0.499 | 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.