Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27816 | 83671;83672;83673 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| N2AB | 26175 | 78748;78749;78750 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| N2A | 25248 | 75967;75968;75969 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| N2B | 18751 | 56476;56477;56478 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| Novex-1 | 18876 | 56851;56852;56853 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| Novex-2 | 18943 | 57052;57053;57054 | chr2:178562686;178562685;178562684 | chr2:179427413;179427412;179427411 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs1250426493  |
None | 0.062 | N | 0.488 | 0.262 | 0.564503807532 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | None | None | None | N | 0.17 | 0.168 | 0.12205267543 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2502 | likely_benign | 0.25 | benign | -1.783 | Destabilizing | 0.035 | N | 0.491 | neutral | None | None | None | None | N |
| I/C | 0.561 | ambiguous | 0.5857 | pathogenic | -1.247 | Destabilizing | 0.824 | D | 0.574 | neutral | None | None | None | None | N |
| I/D | 0.8383 | likely_pathogenic | 0.882 | pathogenic | -1.017 | Destabilizing | 0.555 | D | 0.645 | neutral | None | None | None | None | N |
| I/E | 0.736 | likely_pathogenic | 0.7929 | pathogenic | -0.929 | Destabilizing | 0.555 | D | 0.628 | neutral | None | None | None | None | N |
| I/F | 0.2321 | likely_benign | 0.2638 | benign | -1.109 | Destabilizing | 0.317 | N | 0.525 | neutral | N | 0.475997461 | None | None | N |
| I/G | 0.6671 | likely_pathogenic | 0.6796 | pathogenic | -2.181 | Highly Destabilizing | 0.555 | D | 0.615 | neutral | None | None | None | None | N |
| I/H | 0.6691 | likely_pathogenic | 0.7421 | pathogenic | -1.257 | Destabilizing | 0.935 | D | 0.656 | neutral | None | None | None | None | N |
| I/K | 0.6695 | likely_pathogenic | 0.758 | pathogenic | -1.17 | Destabilizing | 0.555 | D | 0.628 | neutral | None | None | None | None | N |
| I/L | 0.1253 | likely_benign | 0.1293 | benign | -0.726 | Destabilizing | 0.012 | N | 0.332 | neutral | N | 0.41044726 | None | None | N |
| I/M | 0.1179 | likely_benign | 0.1237 | benign | -0.699 | Destabilizing | 0.317 | N | 0.552 | neutral | N | 0.490737627 | None | None | N |
| I/N | 0.4286 | ambiguous | 0.474 | ambiguous | -1.221 | Destabilizing | 0.741 | D | 0.666 | neutral | N | 0.47188899 | None | None | N |
| I/P | 0.9186 | likely_pathogenic | 0.9129 | pathogenic | -1.049 | Destabilizing | 0.555 | D | 0.653 | neutral | None | None | None | None | N |
| I/Q | 0.5959 | likely_pathogenic | 0.6647 | pathogenic | -1.249 | Destabilizing | 0.791 | D | 0.663 | neutral | None | None | None | None | N |
| I/R | 0.5906 | likely_pathogenic | 0.6926 | pathogenic | -0.707 | Destabilizing | 0.555 | D | 0.668 | neutral | None | None | None | None | N |
| I/S | 0.3256 | likely_benign | 0.3502 | ambiguous | -1.939 | Destabilizing | 0.317 | N | 0.6 | neutral | N | 0.503608137 | None | None | N |
| I/T | 0.2576 | likely_benign | 0.2615 | benign | -1.708 | Destabilizing | 0.062 | N | 0.488 | neutral | N | 0.514555849 | None | None | N |
| I/V | 0.0541 | likely_benign | 0.0528 | benign | -1.049 | Destabilizing | None | N | 0.17 | neutral | N | 0.324695144 | None | None | N |
| I/W | 0.891 | likely_pathogenic | 0.9234 | pathogenic | -1.21 | Destabilizing | 0.935 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/Y | 0.6323 | likely_pathogenic | 0.7101 | pathogenic | -0.957 | Destabilizing | 0.555 | D | 0.578 | 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.