Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15689 | 47290;47291;47292 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| N2AB | 14048 | 42367;42368;42369 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| N2A | 13121 | 39586;39587;39588 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| N2B | 6624 | 20095;20096;20097 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| Novex-1 | 6749 | 20470;20471;20472 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| Novex-2 | 6816 | 20671;20672;20673 | chr2:178618393;178618392;178618391 | chr2:179483120;179483119;179483118 |
| 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/L | rs780698011  |
-1.077 | 0.889 | N | 0.494 | 0.174 | 0.593972321423 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| I/L | rs780698011 |
-1.077 | 0.889 | N | 0.494 | 0.174 | 0.593972321423 | gnomAD-4.0.0 | 4.10825E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.9583E-05 | 0 |
| I/N | None | None | 0.999 | D | 0.84 | 0.57 | 0.874120574325 | gnomAD-4.0.0 | 1.59395E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86264E-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 | 0.957 | likely_pathogenic | 0.9587 | pathogenic | -2.295 | Highly Destabilizing | 0.992 | D | 0.694 | prob.neutral | None | None | None | None | I |
| I/C | 0.9672 | likely_pathogenic | 0.9661 | pathogenic | -1.428 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | I |
| I/D | 0.9956 | likely_pathogenic | 0.9951 | pathogenic | -2.021 | Highly Destabilizing | 1.0 | D | 0.836 | deleterious | None | None | None | None | I |
| I/E | 0.9882 | likely_pathogenic | 0.9857 | pathogenic | -1.919 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| I/F | 0.8814 | likely_pathogenic | 0.8651 | pathogenic | -1.507 | Destabilizing | 0.998 | D | 0.766 | deleterious | D | 0.674002715 | None | None | I |
| I/G | 0.9887 | likely_pathogenic | 0.989 | pathogenic | -2.732 | Highly Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| I/H | 0.9919 | likely_pathogenic | 0.991 | pathogenic | -1.975 | Destabilizing | 1.0 | D | 0.803 | deleterious | None | None | None | None | I |
| I/K | 0.9773 | likely_pathogenic | 0.9722 | pathogenic | -1.656 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| I/L | 0.3597 | ambiguous | 0.4477 | ambiguous | -1.097 | Destabilizing | 0.889 | D | 0.494 | neutral | N | 0.491594402 | None | None | I |
| I/M | 0.4373 | ambiguous | 0.4854 | ambiguous | -0.832 | Destabilizing | 0.998 | D | 0.723 | prob.delet. | D | 0.715830699 | None | None | I |
| I/N | 0.9184 | likely_pathogenic | 0.9093 | pathogenic | -1.646 | Destabilizing | 0.999 | D | 0.84 | deleterious | D | 0.695651165 | None | None | I |
| I/P | 0.9393 | likely_pathogenic | 0.9262 | pathogenic | -1.47 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| I/Q | 0.9835 | likely_pathogenic | 0.981 | pathogenic | -1.715 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| I/R | 0.9746 | likely_pathogenic | 0.9684 | pathogenic | -1.116 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| I/S | 0.9681 | likely_pathogenic | 0.9656 | pathogenic | -2.348 | Highly Destabilizing | 0.998 | D | 0.796 | deleterious | D | 0.752197119 | None | None | I |
| I/T | 0.9361 | likely_pathogenic | 0.9285 | pathogenic | -2.119 | Highly Destabilizing | 0.989 | D | 0.812 | deleterious | D | 0.665836147 | None | None | I |
| I/V | 0.1281 | likely_benign | 0.1429 | benign | -1.47 | Destabilizing | 0.333 | N | 0.273 | neutral | N | 0.489538534 | None | None | I |
| I/W | 0.9949 | likely_pathogenic | 0.9953 | pathogenic | -1.72 | Destabilizing | 1.0 | D | 0.768 | deleterious | None | None | None | None | I |
| I/Y | 0.9787 | likely_pathogenic | 0.9745 | pathogenic | -1.483 | Destabilizing | 1.0 | D | 0.787 | deleterious | 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.