Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32648 | 98167;98168;98169 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| N2AB | 31007 | 93244;93245;93246 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| N2A | 30080 | 90463;90464;90465 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| N2B | 23583 | 70972;70973;70974 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| Novex-1 | 23708 | 71347;71348;71349 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| Novex-2 | 23775 | 71548;71549;71550 | chr2:178540224;178540223;178540222 | chr2:179404951;179404950;179404949 |
| 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/N | rs775309560  |
-0.56 | 1.0 | D | 0.721 | 0.366 | None | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| T/N | rs775309560 |
-0.56 | 1.0 | D | 0.721 | 0.366 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | rs775309560 |
-0.56 | 1.0 | D | 0.721 | 0.366 | None | gnomAD-4.0.0 | 1.42537E-05 | None | None | None | None | N | None | 4.00769E-05 | 1.66728E-05 | None | 0 | 0 | None | 0 | 0 | 1.52572E-05 | 0 | 1.60118E-05 |
| T/P | rs762198397 |
-0.298 | 1.0 | N | 0.721 | 0.525 | 0.500488203797 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| T/P | rs762198397 |
-0.298 | 1.0 | N | 0.721 | 0.525 | 0.500488203797 | gnomAD-4.0.0 | 1.59116E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85824E-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 | 0.1244 | likely_benign | 0.1514 | benign | -0.697 | Destabilizing | 0.999 | D | 0.551 | neutral | N | 0.505165575 | None | None | N |
| T/C | 0.4454 | ambiguous | 0.5171 | ambiguous | -0.364 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| T/D | 0.5753 | likely_pathogenic | 0.6703 | pathogenic | -0.072 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| T/E | 0.3218 | likely_benign | 0.3893 | ambiguous | -0.092 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| T/F | 0.3004 | likely_benign | 0.3832 | ambiguous | -0.806 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| T/G | 0.3891 | ambiguous | 0.4424 | ambiguous | -0.932 | Destabilizing | 1.0 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/H | 0.2745 | likely_benign | 0.3565 | ambiguous | -1.146 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | N |
| T/I | 0.1404 | likely_benign | 0.1682 | benign | -0.169 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | N | 0.441039525 | None | None | N |
| T/K | 0.224 | likely_benign | 0.3098 | benign | -0.718 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| T/L | 0.0956 | likely_benign | 0.1161 | benign | -0.169 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| T/M | 0.0841 | likely_benign | 0.1005 | benign | 0.048 | Stabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| T/N | 0.1563 | likely_benign | 0.1943 | benign | -0.557 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | D | 0.523057902 | None | None | N |
| T/P | 0.7337 | likely_pathogenic | 0.7941 | pathogenic | -0.313 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | N | 0.505615512 | None | None | N |
| T/Q | 0.1941 | likely_benign | 0.2437 | benign | -0.718 | Destabilizing | 1.0 | D | 0.732 | prob.delet. | None | None | None | None | N |
| T/R | 0.2115 | likely_benign | 0.3151 | benign | -0.432 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/S | 0.17 | likely_benign | 0.2071 | benign | -0.818 | Destabilizing | 0.999 | D | 0.546 | neutral | N | 0.485214377 | None | None | N |
| T/V | 0.119 | likely_benign | 0.1356 | benign | -0.313 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | N |
| T/W | 0.614 | likely_pathogenic | 0.7104 | pathogenic | -0.768 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| T/Y | 0.3173 | likely_benign | 0.3993 | ambiguous | -0.547 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | 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.