Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21263 | 64012;64013;64014 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| N2AB | 19622 | 59089;59090;59091 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| N2A | 18695 | 56308;56309;56310 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| N2B | 12198 | 36817;36818;36819 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| Novex-1 | 12323 | 37192;37193;37194 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| Novex-2 | 12390 | 37393;37394;37395 | chr2:178587522;178587521;178587520 | chr2:179452249;179452248;179452247 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/G | None | None | 1.0 | D | 0.815 | 0.825 | 0.93082256464 | gnomAD-4.0.0 | 1.60281E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87806E-06 | 0 | 0 |
| V/I | rs1298535121  |
-0.75 | 0.997 | D | 0.733 | 0.539 | 0.79560923071 | gnomAD-2.1.1 | 4.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.03E-06 | 0 |
| V/I | rs1298535121 |
-0.75 | 0.997 | D | 0.733 | 0.539 | 0.79560923071 | gnomAD-4.0.0 | 3.20539E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.87776E-06 | 1.44292E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9712 | likely_pathogenic | 0.9776 | pathogenic | -1.821 | Destabilizing | 0.999 | D | 0.757 | deleterious | D | 0.644985105 | None | None | N |
| V/C | 0.9816 | likely_pathogenic | 0.9856 | pathogenic | -1.915 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| V/D | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -2.154 | Highly Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| V/E | 0.9967 | likely_pathogenic | 0.9966 | pathogenic | -2.105 | Highly Destabilizing | 1.0 | D | 0.839 | deleterious | D | 0.645590518 | None | None | N |
| V/F | 0.9845 | likely_pathogenic | 0.9864 | pathogenic | -1.488 | Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| V/G | 0.9712 | likely_pathogenic | 0.9731 | pathogenic | -2.151 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | D | 0.645590518 | None | None | N |
| V/H | 0.9991 | likely_pathogenic | 0.9992 | pathogenic | -1.568 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| V/I | 0.1797 | likely_benign | 0.1949 | benign | -0.979 | Destabilizing | 0.997 | D | 0.733 | prob.delet. | D | 0.526817543 | None | None | N |
| V/K | 0.9978 | likely_pathogenic | 0.9977 | pathogenic | -1.468 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| V/L | 0.9532 | likely_pathogenic | 0.9607 | pathogenic | -0.979 | Destabilizing | 0.997 | D | 0.763 | deleterious | D | 0.626947702 | None | None | N |
| V/M | 0.9598 | likely_pathogenic | 0.9687 | pathogenic | -1.105 | Destabilizing | 1.0 | D | 0.894 | deleterious | None | None | None | None | N |
| V/N | 0.9933 | likely_pathogenic | 0.9935 | pathogenic | -1.514 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| V/P | 0.9939 | likely_pathogenic | 0.9956 | pathogenic | -1.23 | Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| V/Q | 0.997 | likely_pathogenic | 0.9971 | pathogenic | -1.685 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| V/R | 0.9949 | likely_pathogenic | 0.9948 | pathogenic | -0.999 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/S | 0.9842 | likely_pathogenic | 0.9858 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| V/T | 0.9672 | likely_pathogenic | 0.9707 | pathogenic | -1.925 | Destabilizing | 0.999 | D | 0.826 | deleterious | None | None | None | None | N |
| V/W | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -1.65 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| V/Y | 0.9976 | likely_pathogenic | 0.9978 | pathogenic | -1.336 | Destabilizing | 1.0 | D | 0.885 | 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.