Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35026 | 105301;105302;105303 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| N2AB | 33385 | 100378;100379;100380 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| N2A | 32458 | 97597;97598;97599 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| N2B | 25961 | 78106;78107;78108 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| Novex-1 | 26086 | 78481;78482;78483 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| Novex-2 | 26153 | 78682;78683;78684 | chr2:178531539;178531538;178531537 | chr2:179396266;179396265;179396264 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs757648598  |
0.16 | 1.0 | D | 0.804 | 0.348 | 0.671143324981 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| Y/C | rs757648598 |
0.16 | 1.0 | D | 0.804 | 0.348 | 0.671143324981 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| Y/C | rs757648598 |
0.16 | 1.0 | D | 0.804 | 0.348 | 0.671143324981 | gnomAD-4.0.0 | 7.43567E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01705E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.9276 | likely_pathogenic | 0.9332 | pathogenic | -1.032 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| Y/C | 0.7502 | likely_pathogenic | 0.7602 | pathogenic | 0.307 | Stabilizing | 1.0 | D | 0.804 | deleterious | D | 0.529883166 | None | None | N |
| Y/D | 0.8518 | likely_pathogenic | 0.8554 | pathogenic | 0.401 | Stabilizing | 1.0 | D | 0.783 | deleterious | N | 0.469333353 | None | None | N |
| Y/E | 0.9643 | likely_pathogenic | 0.9666 | pathogenic | 0.384 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| Y/F | 0.1847 | likely_benign | 0.1952 | benign | -0.601 | Destabilizing | 0.434 | N | 0.37 | neutral | N | 0.46793063 | None | None | N |
| Y/G | 0.9186 | likely_pathogenic | 0.924 | pathogenic | -1.259 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| Y/H | 0.7835 | likely_pathogenic | 0.781 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | N | 0.476934116 | None | None | N |
| Y/I | 0.8845 | likely_pathogenic | 0.8987 | pathogenic | -0.427 | Destabilizing | 0.999 | D | 0.732 | prob.delet. | None | None | None | None | N |
| Y/K | 0.9696 | likely_pathogenic | 0.9709 | pathogenic | 0.121 | Stabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | N |
| Y/L | 0.8507 | likely_pathogenic | 0.8666 | pathogenic | -0.427 | Destabilizing | 0.994 | D | 0.633 | neutral | None | None | None | None | N |
| Y/M | 0.9185 | likely_pathogenic | 0.9258 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| Y/N | 0.7334 | likely_pathogenic | 0.7432 | pathogenic | 0.112 | Stabilizing | 1.0 | D | 0.793 | deleterious | N | 0.435375495 | None | None | N |
| Y/P | 0.9914 | likely_pathogenic | 0.9919 | pathogenic | -0.612 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| Y/Q | 0.9631 | likely_pathogenic | 0.9648 | pathogenic | 0.065 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| Y/R | 0.9251 | likely_pathogenic | 0.9292 | pathogenic | 0.458 | Stabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | N |
| Y/S | 0.7099 | likely_pathogenic | 0.7278 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.382829089 | None | None | N |
| Y/T | 0.8589 | likely_pathogenic | 0.8629 | pathogenic | -0.225 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| Y/V | 0.7951 | likely_pathogenic | 0.8091 | pathogenic | -0.612 | Destabilizing | 0.997 | D | 0.716 | prob.delet. | None | None | None | None | N |
| Y/W | 0.7595 | likely_pathogenic | 0.7614 | pathogenic | -0.624 | Destabilizing | 1.0 | D | 0.692 | prob.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.