Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9248 | 27967;27968;27969 | chr2:178712088;178712087;178712086 | chr2:179576815;179576814;179576813 |
| N2AB | 8931 | 27016;27017;27018 | chr2:178712088;178712087;178712086 | chr2:179576815;179576814;179576813 |
| N2A | 8004 | 24235;24236;24237 | chr2:178712088;178712087;178712086 | chr2:179576815;179576814;179576813 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs397517523  |
-0.126 | 0.379 | N | 0.263 | 0.203 | 0.288727942641 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| T/I | rs397517523 |
-0.126 | 0.379 | N | 0.263 | 0.203 | 0.288727942641 | gnomAD-4.0.0 | 6.84213E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99473E-07 | 0 | 0 |
| T/N | rs397517523 |
None | 0.379 | N | 0.358 | 0.154 | 0.216624796971 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | rs397517523 |
None | 0.379 | N | 0.358 | 0.154 | 0.216624796971 | gnomAD-4.0.0 | 6.81618E-06 | None | None | None | None | N | None | 1.33287E-05 | 0 | None | 0 | 2.22886E-05 | None | 0 | 0 | 5.08569E-06 | 0 | 4.80169E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0829 | likely_benign | 0.1054 | benign | -0.538 | Destabilizing | 0.201 | N | 0.374 | neutral | N | 0.45738191 | None | None | N |
| T/C | 0.5699 | likely_pathogenic | 0.6931 | pathogenic | -0.297 | Destabilizing | 0.992 | D | 0.286 | neutral | None | None | None | None | N |
| T/D | 0.4484 | ambiguous | 0.5855 | pathogenic | 0.184 | Stabilizing | 0.617 | D | 0.31 | neutral | None | None | None | None | N |
| T/E | 0.4768 | ambiguous | 0.6319 | pathogenic | 0.145 | Stabilizing | 0.617 | D | 0.281 | neutral | None | None | None | None | N |
| T/F | 0.4402 | ambiguous | 0.5965 | pathogenic | -0.821 | Destabilizing | 0.92 | D | 0.399 | neutral | None | None | None | None | N |
| T/G | 0.1931 | likely_benign | 0.2535 | benign | -0.73 | Destabilizing | 0.447 | N | 0.296 | neutral | None | None | None | None | N |
| T/H | 0.3971 | ambiguous | 0.5162 | ambiguous | -0.958 | Destabilizing | 0.977 | D | 0.369 | neutral | None | None | None | None | N |
| T/I | 0.3894 | ambiguous | 0.5272 | ambiguous | -0.136 | Destabilizing | 0.379 | N | 0.263 | neutral | N | 0.504213065 | None | None | N |
| T/K | 0.3564 | ambiguous | 0.4916 | ambiguous | -0.505 | Destabilizing | 0.447 | N | 0.316 | neutral | None | None | None | None | N |
| T/L | 0.1792 | likely_benign | 0.2733 | benign | -0.136 | Destabilizing | 0.25 | N | 0.299 | neutral | None | None | None | None | N |
| T/M | 0.1288 | likely_benign | 0.1873 | benign | -0.02 | Destabilizing | 0.92 | D | 0.287 | neutral | None | None | None | None | N |
| T/N | 0.1324 | likely_benign | 0.179 | benign | -0.331 | Destabilizing | 0.379 | N | 0.358 | neutral | N | 0.454725607 | None | None | N |
| T/P | 0.3287 | likely_benign | 0.4478 | ambiguous | -0.239 | Destabilizing | 0.896 | D | 0.321 | neutral | N | 0.508810808 | None | None | N |
| T/Q | 0.336 | likely_benign | 0.4552 | ambiguous | -0.49 | Destabilizing | 0.85 | D | 0.313 | neutral | None | None | None | None | N |
| T/R | 0.2935 | likely_benign | 0.4374 | ambiguous | -0.244 | Destabilizing | 0.85 | D | 0.324 | neutral | None | None | None | None | N |
| T/S | 0.0908 | likely_benign | 0.112 | benign | -0.574 | Destabilizing | 0.007 | N | 0.197 | neutral | N | 0.380398419 | None | None | N |
| T/V | 0.2531 | likely_benign | 0.3467 | ambiguous | -0.239 | Destabilizing | 0.021 | N | 0.295 | neutral | None | None | None | None | N |
| T/W | 0.8 | likely_pathogenic | 0.9028 | pathogenic | -0.815 | Destabilizing | 0.992 | D | 0.475 | neutral | None | None | None | None | N |
| T/Y | 0.5239 | ambiguous | 0.6879 | pathogenic | -0.56 | Destabilizing | 0.972 | D | 0.384 | 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.