Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21237 | 63934;63935;63936 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| N2AB | 19596 | 59011;59012;59013 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| N2A | 18669 | 56230;56231;56232 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| N2B | 12172 | 36739;36740;36741 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| Novex-1 | 12297 | 37114;37115;37116 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| Novex-2 | 12364 | 37315;37316;37317 | chr2:178587600;178587599;178587598 | chr2:179452327;179452326;179452325 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs766847414  |
-0.54 | 0.962 | N | 0.497 | 0.282 | 0.346544149963 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| T/A | rs766847414 |
-0.54 | 0.962 | N | 0.497 | 0.282 | 0.346544149963 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| T/A | rs766847414 |
-0.54 | 0.962 | N | 0.497 | 0.282 | 0.346544149963 | gnomAD-4.0.0 | 4.34125E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93555E-06 | 0 | 0 |
| T/I | None | None | 0.999 | N | 0.803 | 0.418 | 0.541962755691 | gnomAD-4.0.0 | 1.20033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.31252E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1237 | likely_benign | 0.1339 | benign | -0.668 | Destabilizing | 0.962 | D | 0.497 | neutral | N | 0.508507816 | None | None | N |
| T/C | 0.4061 | ambiguous | 0.4553 | ambiguous | -0.35 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| T/D | 0.3514 | ambiguous | 0.3908 | ambiguous | -0.46 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| T/E | 0.3981 | ambiguous | 0.4288 | ambiguous | -0.516 | Destabilizing | 0.998 | D | 0.665 | neutral | None | None | None | None | N |
| T/F | 0.4746 | ambiguous | 0.5146 | ambiguous | -1.088 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| T/G | 0.1966 | likely_benign | 0.2334 | benign | -0.838 | Destabilizing | 0.994 | D | 0.615 | neutral | None | None | None | None | N |
| T/H | 0.3091 | likely_benign | 0.3283 | benign | -1.245 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | N |
| T/I | 0.3891 | ambiguous | 0.4287 | ambiguous | -0.322 | Destabilizing | 0.999 | D | 0.803 | deleterious | N | 0.491012382 | None | None | N |
| T/K | 0.2742 | likely_benign | 0.2812 | benign | -0.565 | Destabilizing | 0.998 | D | 0.669 | neutral | None | None | None | None | N |
| T/L | 0.1602 | likely_benign | 0.1736 | benign | -0.322 | Destabilizing | 0.997 | D | 0.581 | neutral | None | None | None | None | N |
| T/M | 0.1523 | likely_benign | 0.1628 | benign | 0.195 | Stabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | N |
| T/N | 0.1078 | likely_benign | 0.1149 | benign | -0.424 | Destabilizing | 0.998 | D | 0.698 | prob.neutral | N | 0.442245539 | None | None | N |
| T/P | 0.6009 | likely_pathogenic | 0.6099 | pathogenic | -0.408 | Destabilizing | 0.999 | D | 0.802 | deleterious | N | 0.511838889 | None | None | N |
| T/Q | 0.2503 | likely_benign | 0.2587 | benign | -0.77 | Destabilizing | 0.999 | D | 0.819 | deleterious | None | None | None | None | N |
| T/R | 0.2553 | likely_benign | 0.2534 | benign | -0.22 | Destabilizing | 0.999 | D | 0.802 | deleterious | None | None | None | None | N |
| T/S | 0.0852 | likely_benign | 0.0942 | benign | -0.63 | Destabilizing | 0.825 | D | 0.353 | neutral | N | 0.503485999 | None | None | N |
| T/V | 0.2353 | likely_benign | 0.263 | benign | -0.408 | Destabilizing | 0.997 | D | 0.557 | neutral | None | None | None | None | N |
| T/W | 0.8178 | likely_pathogenic | 0.8425 | pathogenic | -1.015 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | N |
| T/Y | 0.5118 | ambiguous | 0.5525 | ambiguous | -0.751 | Destabilizing | 1.0 | D | 0.854 | deleterious | 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.