Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27976 | 84151;84152;84153 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| N2AB | 26335 | 79228;79229;79230 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| N2A | 25408 | 76447;76448;76449 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| N2B | 18911 | 56956;56957;56958 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| Novex-1 | 19036 | 57331;57332;57333 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| Novex-2 | 19103 | 57532;57533;57534 | chr2:178562206;178562205;178562204 | chr2:179426933;179426932;179426931 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.958 | N | 0.483 | 0.304 | 0.191931220699 | gnomAD-4.0.0 | 4.8013E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.25002E-06 | 0 | 0 |
| A/T | rs879219359  |
-1.44 | 0.958 | N | 0.677 | 0.317 | None | 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 |
| A/T | rs879219359 |
-1.44 | 0.958 | N | 0.677 | 0.317 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs879219359 |
-1.44 | 0.958 | N | 0.677 | 0.317 | None | gnomAD-4.0.0 | 1.11628E-05 | None | None | None | None | N | None | 1.33668E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44142E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6287 | likely_pathogenic | 0.6085 | pathogenic | -0.865 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| A/D | 0.5239 | ambiguous | 0.6261 | pathogenic | -1.083 | Destabilizing | 0.142 | N | 0.399 | neutral | N | 0.474583291 | None | None | N |
| A/E | 0.3555 | ambiguous | 0.4288 | ambiguous | -1.199 | Destabilizing | 0.938 | D | 0.611 | neutral | None | None | None | None | N |
| A/F | 0.49 | ambiguous | 0.5393 | ambiguous | -1.147 | Destabilizing | 0.998 | D | 0.745 | deleterious | None | None | None | None | N |
| A/G | 0.182 | likely_benign | 0.1842 | benign | -0.95 | Destabilizing | 0.958 | D | 0.483 | neutral | N | 0.492941035 | None | None | N |
| A/H | 0.6877 | likely_pathogenic | 0.7206 | pathogenic | -1.022 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| A/I | 0.3956 | ambiguous | 0.3976 | ambiguous | -0.601 | Destabilizing | 0.995 | D | 0.729 | prob.delet. | None | None | None | None | N |
| A/K | 0.6212 | likely_pathogenic | 0.6758 | pathogenic | -1.193 | Destabilizing | 0.991 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/L | 0.3273 | likely_benign | 0.3649 | ambiguous | -0.601 | Destabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | N |
| A/M | 0.3765 | ambiguous | 0.3787 | ambiguous | -0.459 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| A/N | 0.4091 | ambiguous | 0.433 | ambiguous | -0.812 | Destabilizing | 0.982 | D | 0.699 | prob.neutral | None | None | None | None | N |
| A/P | 0.6222 | likely_pathogenic | 0.6651 | pathogenic | -0.632 | Destabilizing | 0.994 | D | 0.731 | prob.delet. | N | 0.459579681 | None | None | N |
| A/Q | 0.4662 | ambiguous | 0.4866 | ambiguous | -1.102 | Destabilizing | 0.995 | D | 0.757 | deleterious | None | None | None | None | N |
| A/R | 0.5712 | likely_pathogenic | 0.615 | pathogenic | -0.674 | Destabilizing | 0.995 | D | 0.745 | deleterious | None | None | None | None | N |
| A/S | 0.113 | likely_benign | 0.1112 | benign | -1.046 | Destabilizing | 0.958 | D | 0.479 | neutral | N | 0.480856202 | None | None | N |
| A/T | 0.1606 | likely_benign | 0.1803 | benign | -1.091 | Destabilizing | 0.958 | D | 0.677 | prob.neutral | N | 0.468796393 | None | None | N |
| A/V | 0.1791 | likely_benign | 0.1817 | benign | -0.632 | Destabilizing | 0.979 | D | 0.661 | neutral | N | 0.454090888 | None | None | N |
| A/W | 0.8685 | likely_pathogenic | 0.8909 | pathogenic | -1.333 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| A/Y | 0.6199 | likely_pathogenic | 0.6606 | pathogenic | -1.012 | Destabilizing | 1.0 | D | 0.736 | prob.delet. | 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.