Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16307 | 49144;49145;49146 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| N2AB | 14666 | 44221;44222;44223 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| N2A | 13739 | 41440;41441;41442 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| N2B | 7242 | 21949;21950;21951 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| Novex-1 | 7367 | 22324;22325;22326 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| Novex-2 | 7434 | 22525;22526;22527 | chr2:178614595;178614594;178614593 | chr2:179479322;179479321;179479320 |
| 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/M | rs755394057  |
None | 0.817 | D | 0.411 | 0.208 | 0.564798353577 | gnomAD-4.0.0 | 6.84721E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65887E-05 |
| I/T | None | None | 0.99 | D | 0.618 | 0.615 | 0.792523853362 | gnomAD-4.0.0 | 2.7389E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59955E-06 | 0 | 0 |
| I/V | rs1559813119 |
None | 0.817 | N | 0.423 | 0.145 | 0.603487413129 | 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 |
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 | 0.4334 | ambiguous | 0.5003 | ambiguous | -1.853 | Destabilizing | 0.985 | D | 0.531 | neutral | None | None | None | None | N |
| I/C | 0.8307 | likely_pathogenic | 0.8384 | pathogenic | -1.196 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| I/D | 0.971 | likely_pathogenic | 0.9802 | pathogenic | -1.463 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| I/E | 0.8706 | likely_pathogenic | 0.8974 | pathogenic | -1.469 | Destabilizing | 0.999 | D | 0.728 | prob.delet. | None | None | None | None | N |
| I/F | 0.2419 | likely_benign | 0.2898 | benign | -1.509 | Destabilizing | 0.135 | N | 0.376 | neutral | D | 0.558057867 | None | None | N |
| I/G | 0.9045 | likely_pathogenic | 0.9274 | pathogenic | -2.178 | Highly Destabilizing | 0.998 | D | 0.714 | prob.delet. | None | None | None | None | N |
| I/H | 0.8468 | likely_pathogenic | 0.8781 | pathogenic | -1.451 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| I/K | 0.7171 | likely_pathogenic | 0.7635 | pathogenic | -1.191 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/L | 0.1952 | likely_benign | 0.219 | benign | -1.028 | Destabilizing | 0.817 | D | 0.368 | neutral | N | 0.507979455 | None | None | N |
| I/M | 0.1123 | likely_benign | 0.1339 | benign | -0.752 | Destabilizing | 0.817 | D | 0.411 | neutral | D | 0.549617585 | None | None | N |
| I/N | 0.7983 | likely_pathogenic | 0.8361 | pathogenic | -0.981 | Destabilizing | 0.999 | D | 0.762 | deleterious | D | 0.620222758 | None | None | N |
| I/P | 0.9578 | likely_pathogenic | 0.9718 | pathogenic | -1.273 | Destabilizing | 0.999 | D | 0.765 | deleterious | None | None | None | None | N |
| I/Q | 0.7523 | likely_pathogenic | 0.7942 | pathogenic | -1.209 | Destabilizing | 0.998 | D | 0.765 | deleterious | None | None | None | None | N |
| I/R | 0.6296 | likely_pathogenic | 0.6916 | pathogenic | -0.587 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| I/S | 0.618 | likely_pathogenic | 0.6903 | pathogenic | -1.597 | Destabilizing | 0.997 | D | 0.665 | neutral | D | 0.596963925 | None | None | N |
| I/T | 0.2282 | likely_benign | 0.272 | benign | -1.486 | Destabilizing | 0.99 | D | 0.618 | neutral | D | 0.570664738 | None | None | N |
| I/V | 0.0712 | likely_benign | 0.0742 | benign | -1.273 | Destabilizing | 0.817 | D | 0.423 | neutral | N | 0.497510192 | None | None | N |
| I/W | 0.8495 | likely_pathogenic | 0.8887 | pathogenic | -1.566 | Destabilizing | 1.0 | D | 0.756 | deleterious | None | None | None | None | N |
| I/Y | 0.7538 | likely_pathogenic | 0.7898 | pathogenic | -1.335 | Destabilizing | 0.991 | D | 0.662 | 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.