Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31539 | 94840;94841;94842 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| N2AB | 29898 | 89917;89918;89919 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| N2A | 28971 | 87136;87137;87138 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| N2B | 22474 | 67645;67646;67647 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| Novex-1 | 22599 | 68020;68021;68022 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| Novex-2 | 22666 | 68221;68222;68223 | chr2:178546813;178546812;178546811 | chr2:179411540;179411539;179411538 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs1697378195  |
None | 0.296 | N | 0.489 | 0.224 | 0.50557994651 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| V/A | rs1697378195 |
None | 0.296 | N | 0.489 | 0.224 | 0.50557994651 | gnomAD-4.0.0 | 6.5722E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.07039E-04 | 0 |
| V/E | None | None | 0.879 | N | 0.69 | 0.381 | 0.614395592218 | gnomAD-4.0.0 | 1.59407E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86544E-06 | 0 | 0 |
| V/M | rs1403013054 |
None | 0.782 | N | 0.552 | 0.191 | 0.451213972277 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/M | rs1403013054 |
None | 0.782 | N | 0.552 | 0.191 | 0.451213972277 | gnomAD-4.0.0 | 3.84893E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.85437E-05 | None | 0 | 0 | 2.39831E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2501 | likely_benign | 0.225 | benign | -1.011 | Destabilizing | 0.296 | N | 0.489 | neutral | N | 0.468956845 | None | None | I |
| V/C | 0.8542 | likely_pathogenic | 0.8627 | pathogenic | -0.823 | Destabilizing | 0.991 | D | 0.623 | neutral | None | None | None | None | I |
| V/D | 0.8758 | likely_pathogenic | 0.8706 | pathogenic | -0.491 | Destabilizing | 0.906 | D | 0.726 | prob.delet. | None | None | None | None | I |
| V/E | 0.7668 | likely_pathogenic | 0.7536 | pathogenic | -0.551 | Destabilizing | 0.879 | D | 0.69 | prob.neutral | N | 0.483963583 | None | None | I |
| V/F | 0.4026 | ambiguous | 0.4375 | ambiguous | -0.889 | Destabilizing | 0.826 | D | 0.627 | neutral | None | None | None | None | I |
| V/G | 0.5326 | ambiguous | 0.5143 | ambiguous | -1.244 | Destabilizing | 0.879 | D | 0.678 | prob.neutral | N | 0.498722392 | None | None | I |
| V/H | 0.8981 | likely_pathogenic | 0.8992 | pathogenic | -0.715 | Destabilizing | 0.991 | D | 0.762 | deleterious | None | None | None | None | I |
| V/I | 0.073 | likely_benign | 0.0804 | benign | -0.512 | Destabilizing | 0.004 | N | 0.192 | neutral | None | None | None | None | I |
| V/K | 0.8252 | likely_pathogenic | 0.8269 | pathogenic | -0.798 | Destabilizing | 0.906 | D | 0.695 | prob.neutral | None | None | None | None | I |
| V/L | 0.2723 | likely_benign | 0.2927 | benign | -0.512 | Destabilizing | 0.068 | N | 0.444 | neutral | N | 0.441692886 | None | None | I |
| V/M | 0.2028 | likely_benign | 0.2086 | benign | -0.438 | Destabilizing | 0.782 | D | 0.552 | neutral | N | 0.51084354 | None | None | I |
| V/N | 0.6566 | likely_pathogenic | 0.6534 | pathogenic | -0.549 | Destabilizing | 0.906 | D | 0.732 | prob.delet. | None | None | None | None | I |
| V/P | 0.9304 | likely_pathogenic | 0.9317 | pathogenic | -0.642 | Destabilizing | 0.967 | D | 0.708 | prob.delet. | None | None | None | None | I |
| V/Q | 0.7032 | likely_pathogenic | 0.693 | pathogenic | -0.764 | Destabilizing | 0.967 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/R | 0.7367 | likely_pathogenic | 0.7512 | pathogenic | -0.269 | Destabilizing | 0.906 | D | 0.74 | deleterious | None | None | None | None | I |
| V/S | 0.3829 | ambiguous | 0.34 | ambiguous | -1.059 | Destabilizing | 0.704 | D | 0.567 | neutral | None | None | None | None | I |
| V/T | 0.154 | likely_benign | 0.1418 | benign | -1.01 | Destabilizing | 0.04 | N | 0.283 | neutral | None | None | None | None | I |
| V/W | 0.9492 | likely_pathogenic | 0.9566 | pathogenic | -0.977 | Destabilizing | 0.991 | D | 0.77 | deleterious | None | None | None | None | I |
| V/Y | 0.8618 | likely_pathogenic | 0.872 | pathogenic | -0.695 | Destabilizing | 0.906 | D | 0.625 | 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.