Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21225 | 63898;63899;63900 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| N2AB | 19584 | 58975;58976;58977 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| N2A | 18657 | 56194;56195;56196 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| N2B | 12160 | 36703;36704;36705 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| Novex-1 | 12285 | 37078;37079;37080 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| Novex-2 | 12352 | 37279;37280;37281 | chr2:178587636;178587635;178587634 | chr2:179452363;179452362;179452361 |
| 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 | rs1396646735  |
-0.52 | 0.822 | N | 0.384 | 0.28 | 0.607687067698 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 0 | 0 |
| V/A | rs1396646735 |
-0.52 | 0.822 | N | 0.384 | 0.28 | 0.607687067698 | gnomAD-4.0.0 | 4.10775E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87829E-05 | 0 | 4.49865E-06 | 0 | 0 |
| V/I | rs777568221 |
-0.103 | 0.058 | N | 0.224 | 0.123 | 0.346315397577 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | I | None | 0 | 2.91E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| V/I | rs777568221 |
-0.103 | 0.058 | N | 0.224 | 0.123 | 0.346315397577 | gnomAD-4.0.0 | 3.18719E-06 | None | None | None | None | I | None | 0 | 2.28938E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43349E-05 | 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 | 0.337 | likely_benign | 0.2863 | benign | -0.714 | Destabilizing | 0.822 | D | 0.384 | neutral | N | 0.473509808 | None | None | I |
| V/C | 0.8051 | likely_pathogenic | 0.7902 | pathogenic | -0.627 | Destabilizing | 0.998 | D | 0.529 | neutral | None | None | None | None | I |
| V/D | 0.6461 | likely_pathogenic | 0.5956 | pathogenic | -0.257 | Destabilizing | 0.99 | D | 0.686 | prob.neutral | N | 0.461599304 | None | None | I |
| V/E | 0.5575 | ambiguous | 0.4975 | ambiguous | -0.325 | Destabilizing | 0.978 | D | 0.614 | neutral | None | None | None | None | I |
| V/F | 0.3553 | ambiguous | 0.2921 | benign | -0.692 | Destabilizing | 0.89 | D | 0.502 | neutral | N | 0.50229392 | None | None | I |
| V/G | 0.4207 | ambiguous | 0.3814 | ambiguous | -0.918 | Destabilizing | 0.971 | D | 0.684 | prob.neutral | N | 0.43693572 | None | None | I |
| V/H | 0.7744 | likely_pathogenic | 0.7289 | pathogenic | -0.404 | Destabilizing | 0.998 | D | 0.675 | neutral | None | None | None | None | I |
| V/I | 0.1044 | likely_benign | 0.0887 | benign | -0.303 | Destabilizing | 0.058 | N | 0.224 | neutral | N | 0.437647796 | None | None | I |
| V/K | 0.6367 | likely_pathogenic | 0.5841 | pathogenic | -0.574 | Destabilizing | 0.978 | D | 0.621 | neutral | None | None | None | None | I |
| V/L | 0.3212 | likely_benign | 0.215 | benign | -0.303 | Destabilizing | 0.014 | N | 0.223 | neutral | N | 0.457502993 | None | None | I |
| V/M | 0.2906 | likely_benign | 0.2173 | benign | -0.368 | Destabilizing | 0.956 | D | 0.478 | neutral | None | None | None | None | I |
| V/N | 0.5237 | ambiguous | 0.459 | ambiguous | -0.326 | Destabilizing | 0.993 | D | 0.677 | prob.neutral | None | None | None | None | I |
| V/P | 0.7806 | likely_pathogenic | 0.7488 | pathogenic | -0.404 | Destabilizing | 0.993 | D | 0.619 | neutral | None | None | None | None | I |
| V/Q | 0.555 | ambiguous | 0.5066 | ambiguous | -0.51 | Destabilizing | 0.993 | D | 0.615 | neutral | None | None | None | None | I |
| V/R | 0.5413 | ambiguous | 0.5076 | ambiguous | -0.086 | Destabilizing | 0.978 | D | 0.676 | prob.neutral | None | None | None | None | I |
| V/S | 0.3966 | ambiguous | 0.3625 | ambiguous | -0.772 | Destabilizing | 0.978 | D | 0.626 | neutral | None | None | None | None | I |
| V/T | 0.2998 | likely_benign | 0.263 | benign | -0.729 | Destabilizing | 0.86 | D | 0.373 | neutral | None | None | None | None | I |
| V/W | 0.9018 | likely_pathogenic | 0.8656 | pathogenic | -0.802 | Destabilizing | 0.998 | D | 0.663 | neutral | None | None | None | None | I |
| V/Y | 0.7653 | likely_pathogenic | 0.7189 | pathogenic | -0.505 | Destabilizing | 0.978 | D | 0.502 | 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.