Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18043 | 54352;54353;54354 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| N2AB | 16402 | 49429;49430;49431 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| N2A | 15475 | 46648;46649;46650 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| N2B | 8978 | 27157;27158;27159 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| Novex-1 | 9103 | 27532;27533;27534 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| Novex-2 | 9170 | 27733;27734;27735 | chr2:178605050;178605049;178605048 | chr2:179469777;179469776;179469775 |
| 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/F | None | None | 0.999 | D | 0.691 | 0.777 | 0.68707659006 | 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 |
| Y/H | rs757392311  |
-2.12 | 1.0 | D | 0.799 | 0.862 | 0.75654253001 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.68E-05 | 0 | 0 |
| Y/H | rs757392311 |
-2.12 | 1.0 | D | 0.799 | 0.862 | 0.75654253001 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| Y/H | rs757392311 |
-2.12 | 1.0 | D | 0.799 | 0.862 | 0.75654253001 | gnomAD-4.0.0 | 6.58051E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.41265E-05 | 0 | 0 | 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 | 0.9979 | likely_pathogenic | 0.998 | pathogenic | -2.763 | Highly Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| Y/C | 0.9443 | likely_pathogenic | 0.9545 | pathogenic | -2.512 | Highly Destabilizing | 1.0 | D | 0.845 | deleterious | D | 0.619063027 | None | None | N |
| Y/D | 0.9992 | likely_pathogenic | 0.9992 | pathogenic | -2.854 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | D | 0.635314553 | None | None | N |
| Y/E | 0.9997 | likely_pathogenic | 0.9997 | pathogenic | -2.627 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| Y/F | 0.1538 | likely_benign | 0.1462 | benign | -1.195 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | D | 0.556480371 | None | None | N |
| Y/G | 0.9971 | likely_pathogenic | 0.9973 | pathogenic | -3.214 | Highly Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| Y/H | 0.981 | likely_pathogenic | 0.9818 | pathogenic | -2.224 | Highly Destabilizing | 1.0 | D | 0.799 | deleterious | D | 0.635112749 | None | None | N |
| Y/I | 0.9478 | likely_pathogenic | 0.9559 | pathogenic | -1.278 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| Y/K | 0.9995 | likely_pathogenic | 0.9995 | pathogenic | -2.294 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| Y/L | 0.9175 | likely_pathogenic | 0.9258 | pathogenic | -1.278 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| Y/M | 0.9828 | likely_pathogenic | 0.9841 | pathogenic | -1.458 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| Y/N | 0.9948 | likely_pathogenic | 0.9952 | pathogenic | -3.104 | Highly Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.635314553 | None | None | N |
| Y/P | 0.9995 | likely_pathogenic | 0.9996 | pathogenic | -1.787 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| Y/Q | 0.9994 | likely_pathogenic | 0.9994 | pathogenic | -2.734 | Highly Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| Y/R | 0.9977 | likely_pathogenic | 0.9976 | pathogenic | -2.263 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| Y/S | 0.9954 | likely_pathogenic | 0.9954 | pathogenic | -3.592 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | D | 0.635314553 | None | None | N |
| Y/T | 0.998 | likely_pathogenic | 0.9981 | pathogenic | -3.222 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| Y/V | 0.9252 | likely_pathogenic | 0.9348 | pathogenic | -1.787 | Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| Y/W | 0.6793 | likely_pathogenic | 0.6768 | pathogenic | -0.562 | Destabilizing | 1.0 | D | 0.785 | 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.