Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24335 | 73228;73229;73230 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| N2AB | 22694 | 68305;68306;68307 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| N2A | 21767 | 65524;65525;65526 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| N2B | 15270 | 46033;46034;46035 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| Novex-1 | 15395 | 46408;46409;46410 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| Novex-2 | 15462 | 46609;46610;46611 | chr2:178573129;178573128;178573127 | chr2:179437856;179437855;179437854 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs766442878  |
0.001 | 0.997 | N | 0.787 | 0.26 | 0.368369118721 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/I | rs766442878 |
0.001 | 0.997 | N | 0.787 | 0.26 | 0.368369118721 | gnomAD-4.0.0 | 3.18448E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71961E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1358 | likely_benign | 0.1323 | benign | -0.388 | Destabilizing | 0.898 | D | 0.509 | neutral | N | 0.511168827 | None | None | N |
| T/C | 0.3751 | ambiguous | 0.3766 | ambiguous | -0.702 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| T/D | 0.8529 | likely_pathogenic | 0.8312 | pathogenic | -1.653 | Destabilizing | 0.995 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/E | 0.7708 | likely_pathogenic | 0.7759 | pathogenic | -1.649 | Destabilizing | 0.995 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/F | 0.3718 | ambiguous | 0.3702 | ambiguous | -0.999 | Destabilizing | 0.998 | D | 0.817 | deleterious | None | None | None | None | N |
| T/G | 0.4222 | ambiguous | 0.3953 | ambiguous | -0.564 | Destabilizing | 0.966 | D | 0.635 | neutral | None | None | None | None | N |
| T/H | 0.4114 | ambiguous | 0.3886 | ambiguous | -1.088 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | N |
| T/I | 0.2875 | likely_benign | 0.3101 | benign | -0.017 | Destabilizing | 0.997 | D | 0.787 | deleterious | N | 0.462142729 | None | None | N |
| T/K | 0.5081 | ambiguous | 0.5549 | ambiguous | -0.454 | Destabilizing | 0.993 | D | 0.701 | prob.neutral | N | 0.519326951 | None | None | N |
| T/L | 0.2196 | likely_benign | 0.2337 | benign | -0.017 | Destabilizing | 0.983 | D | 0.603 | neutral | None | None | None | None | N |
| T/M | 0.1454 | likely_benign | 0.1556 | benign | 0.335 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| T/N | 0.3184 | likely_benign | 0.2985 | benign | -0.803 | Destabilizing | 0.995 | D | 0.625 | neutral | None | None | None | None | N |
| T/P | 0.755 | likely_pathogenic | 0.7075 | pathogenic | -0.113 | Destabilizing | 0.997 | D | 0.785 | deleterious | N | 0.481092475 | None | None | N |
| T/Q | 0.4805 | ambiguous | 0.5077 | ambiguous | -1.142 | Destabilizing | 0.998 | D | 0.787 | deleterious | None | None | None | None | N |
| T/R | 0.4457 | ambiguous | 0.471 | ambiguous | -0.184 | Destabilizing | 0.993 | D | 0.783 | deleterious | N | 0.475305577 | None | None | N |
| T/S | 0.1304 | likely_benign | 0.1209 | benign | -0.756 | Destabilizing | 0.362 | N | 0.257 | neutral | N | 0.4843103 | None | None | N |
| T/V | 0.2031 | likely_benign | 0.2185 | benign | -0.113 | Destabilizing | 0.983 | D | 0.511 | neutral | None | None | None | None | N |
| T/W | 0.7765 | likely_pathogenic | 0.7502 | pathogenic | -1.099 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| T/Y | 0.4071 | ambiguous | 0.3893 | ambiguous | -0.66 | Destabilizing | 0.999 | D | 0.815 | 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.