Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16475 | 49648;49649;49650 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| N2AB | 14834 | 44725;44726;44727 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| N2A | 13907 | 41944;41945;41946 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| N2B | 7410 | 22453;22454;22455 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| Novex-1 | 7535 | 22828;22829;22830 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| Novex-2 | 7602 | 23029;23030;23031 | chr2:178613860;178613859;178613858 | chr2:179478587;179478586;179478585 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs1246365092  |
0.638 | 1.0 | N | 0.669 | 0.298 | 0.252162846088 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/N | rs1246365092 |
0.638 | 1.0 | N | 0.669 | 0.298 | 0.252162846088 | gnomAD-4.0.0 | 4.79447E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.30071E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1664 | likely_benign | 0.1338 | benign | -0.017 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | N | 0.46711991 | None | None | I |
| D/C | 0.7066 | likely_pathogenic | 0.6328 | pathogenic | 0.222 | Stabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/E | 0.1421 | likely_benign | 0.1174 | benign | -0.236 | Destabilizing | 1.0 | D | 0.505 | neutral | N | 0.43085393 | None | None | I |
| D/F | 0.6753 | likely_pathogenic | 0.6035 | pathogenic | -0.186 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/G | 0.2635 | likely_benign | 0.2134 | benign | -0.157 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.457123811 | None | None | I |
| D/H | 0.4338 | ambiguous | 0.351 | ambiguous | 0.08 | Stabilizing | 1.0 | D | 0.668 | neutral | N | 0.482506039 | None | None | I |
| D/I | 0.3442 | ambiguous | 0.2894 | benign | 0.286 | Stabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| D/K | 0.3967 | ambiguous | 0.324 | benign | 0.562 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| D/L | 0.3646 | ambiguous | 0.3046 | benign | 0.286 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | I |
| D/M | 0.5722 | likely_pathogenic | 0.4861 | ambiguous | 0.326 | Stabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| D/N | 0.141 | likely_benign | 0.1255 | benign | 0.411 | Stabilizing | 1.0 | D | 0.669 | neutral | N | 0.481028844 | None | None | I |
| D/P | 0.7457 | likely_pathogenic | 0.6467 | pathogenic | 0.206 | Stabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/Q | 0.387 | ambiguous | 0.2997 | benign | 0.4 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/R | 0.4851 | ambiguous | 0.3941 | ambiguous | 0.642 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| D/S | 0.1568 | likely_benign | 0.1333 | benign | 0.311 | Stabilizing | 1.0 | D | 0.7 | prob.neutral | None | None | None | None | I |
| D/T | 0.2488 | likely_benign | 0.1993 | benign | 0.415 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| D/V | 0.1946 | likely_benign | 0.1633 | benign | 0.206 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | N | 0.47783414 | None | None | I |
| D/W | 0.8984 | likely_pathogenic | 0.8554 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/Y | 0.3127 | likely_benign | 0.2771 | benign | 0.04 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.501612672 | 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.