Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26317 | 79174;79175;79176 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| N2AB | 24676 | 74251;74252;74253 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| N2A | 23749 | 71470;71471;71472 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| N2B | 17252 | 51979;51980;51981 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| Novex-1 | 17377 | 52354;52355;52356 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| Novex-2 | 17444 | 52555;52556;52557 | chr2:178567183;178567182;178567181 | chr2:179431910;179431909;179431908 |
| 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/N | rs759942713  |
-0.678 | 0.931 | N | 0.683 | 0.23 | 0.185906805712 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| S/N | rs759942713 |
-0.678 | 0.931 | N | 0.683 | 0.23 | 0.185906805712 | gnomAD-4.0.0 | 4.1068E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39853E-06 | 0 | 0 |
| S/R | None | None | 0.939 | N | 0.683 | 0.324 | 0.301789629655 | gnomAD-4.0.0 | 1.20034E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31253E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0924 | likely_benign | 0.0979 | benign | -0.837 | Destabilizing | 0.016 | N | 0.312 | neutral | None | None | None | None | I |
| S/C | 0.1096 | likely_benign | 0.1119 | benign | -0.472 | Destabilizing | 0.015 | N | 0.499 | neutral | N | 0.520484531 | None | None | I |
| S/D | 0.9057 | likely_pathogenic | 0.9067 | pathogenic | -0.246 | Destabilizing | 0.854 | D | 0.669 | neutral | None | None | None | None | I |
| S/E | 0.9461 | likely_pathogenic | 0.9499 | pathogenic | -0.275 | Destabilizing | 0.854 | D | 0.659 | neutral | None | None | None | None | I |
| S/F | 0.5932 | likely_pathogenic | 0.6491 | pathogenic | -1.18 | Destabilizing | 0.953 | D | 0.697 | prob.neutral | None | None | None | None | I |
| S/G | 0.2027 | likely_benign | 0.2204 | benign | -1.049 | Destabilizing | 0.472 | N | 0.597 | neutral | N | 0.472135118 | None | None | I |
| S/H | 0.8135 | likely_pathogenic | 0.8339 | pathogenic | -1.584 | Destabilizing | 0.996 | D | 0.657 | neutral | None | None | None | None | I |
| S/I | 0.6268 | likely_pathogenic | 0.6918 | pathogenic | -0.381 | Destabilizing | 0.884 | D | 0.703 | prob.neutral | N | 0.501060062 | None | None | I |
| S/K | 0.9831 | likely_pathogenic | 0.9838 | pathogenic | -0.758 | Destabilizing | 0.854 | D | 0.654 | neutral | None | None | None | None | I |
| S/L | 0.2663 | likely_benign | 0.332 | benign | -0.381 | Destabilizing | 0.59 | D | 0.611 | neutral | None | None | None | None | I |
| S/M | 0.4065 | ambiguous | 0.465 | ambiguous | 0.061 | Stabilizing | 0.984 | D | 0.663 | neutral | None | None | None | None | I |
| S/N | 0.4996 | ambiguous | 0.5806 | pathogenic | -0.631 | Destabilizing | 0.931 | D | 0.683 | prob.neutral | N | 0.484437065 | None | None | I |
| S/P | 0.9906 | likely_pathogenic | 0.9907 | pathogenic | -0.501 | Destabilizing | 0.953 | D | 0.68 | prob.neutral | None | None | None | None | I |
| S/Q | 0.8938 | likely_pathogenic | 0.9029 | pathogenic | -0.831 | Destabilizing | 0.984 | D | 0.671 | neutral | None | None | None | None | I |
| S/R | 0.965 | likely_pathogenic | 0.9673 | pathogenic | -0.613 | Destabilizing | 0.939 | D | 0.683 | prob.neutral | N | 0.47730704 | None | None | I |
| S/T | 0.224 | likely_benign | 0.2658 | benign | -0.684 | Destabilizing | 0.472 | N | 0.606 | neutral | N | 0.480891892 | None | None | I |
| S/V | 0.4864 | ambiguous | 0.5532 | ambiguous | -0.501 | Destabilizing | 0.742 | D | 0.645 | neutral | None | None | None | None | I |
| S/W | 0.7699 | likely_pathogenic | 0.7993 | pathogenic | -1.129 | Destabilizing | 0.996 | D | 0.719 | prob.delet. | None | None | None | None | I |
| S/Y | 0.6059 | likely_pathogenic | 0.6776 | pathogenic | -0.885 | Destabilizing | 0.984 | D | 0.691 | prob.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.