Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22969 | 69130;69131;69132 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| N2AB | 21328 | 64207;64208;64209 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| N2A | 20401 | 61426;61427;61428 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| N2B | 13904 | 41935;41936;41937 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| Novex-1 | 14029 | 42310;42311;42312 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| Novex-2 | 14096 | 42511;42512;42513 | chr2:178577430;178577429;178577428 | chr2:179442157;179442156;179442155 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/F | rs771013967  |
None | 0.966 | D | 0.724 | 0.238 | 0.550128394979 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.9425E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/F | rs771013967 |
None | 0.966 | D | 0.724 | 0.238 | 0.550128394979 | gnomAD-4.0.0 | 1.8626E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.71532E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs771013967 |
None | 0.267 | N | 0.469 | 0.104 | 0.593486797142 | gnomAD-4.0.0 | 6.17016E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.77099E-04 | None | 0 | 0 | 9.00703E-07 | 0 | 1.65942E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1683 | likely_benign | 0.1732 | benign | -0.311 | Destabilizing | 0.325 | N | 0.657 | neutral | None | None | None | None | N |
| I/C | 0.5218 | ambiguous | 0.5402 | ambiguous | -0.648 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | N |
| I/D | 0.4278 | ambiguous | 0.4664 | ambiguous | 0.122 | Stabilizing | 0.842 | D | 0.793 | deleterious | None | None | None | None | N |
| I/E | 0.337 | likely_benign | 0.3704 | ambiguous | 0.024 | Stabilizing | 0.842 | D | 0.789 | deleterious | None | None | None | None | N |
| I/F | 0.1422 | likely_benign | 0.1365 | benign | -0.498 | Destabilizing | 0.966 | D | 0.724 | prob.delet. | D | 0.525613497 | None | None | N |
| I/G | 0.3758 | ambiguous | 0.3888 | ambiguous | -0.414 | Destabilizing | 0.842 | D | 0.781 | deleterious | None | None | None | None | N |
| I/H | 0.3101 | likely_benign | 0.3175 | benign | 0.137 | Stabilizing | 0.998 | D | 0.863 | deleterious | None | None | None | None | N |
| I/K | 0.1929 | likely_benign | 0.1936 | benign | -0.097 | Destabilizing | 0.842 | D | 0.794 | deleterious | None | None | None | None | N |
| I/L | 0.1031 | likely_benign | 0.1033 | benign | -0.171 | Destabilizing | 0.267 | N | 0.495 | neutral | N | 0.511470764 | None | None | N |
| I/M | 0.0964 | likely_benign | 0.0987 | benign | -0.359 | Destabilizing | 0.989 | D | 0.633 | neutral | N | 0.504603506 | None | None | N |
| I/N | 0.1338 | likely_benign | 0.1557 | benign | 0.064 | Stabilizing | 0.801 | D | 0.807 | deleterious | N | 0.50114092 | None | None | N |
| I/P | 0.5873 | likely_pathogenic | 0.6334 | pathogenic | -0.188 | Destabilizing | 0.974 | D | 0.832 | deleterious | None | None | None | None | N |
| I/Q | 0.2533 | likely_benign | 0.2694 | benign | -0.115 | Destabilizing | 0.974 | D | 0.848 | deleterious | None | None | None | None | N |
| I/R | 0.178 | likely_benign | 0.1761 | benign | 0.323 | Stabilizing | 0.974 | D | 0.833 | deleterious | None | None | None | None | N |
| I/S | 0.1389 | likely_benign | 0.1531 | benign | -0.366 | Destabilizing | 0.062 | N | 0.541 | neutral | D | 0.527152292 | None | None | N |
| I/T | 0.1033 | likely_benign | 0.1157 | benign | -0.359 | Destabilizing | 0.022 | N | 0.534 | neutral | N | 0.508566531 | None | None | N |
| I/V | 0.0676 | likely_benign | 0.0647 | benign | -0.188 | Destabilizing | 0.267 | N | 0.469 | neutral | N | 0.45530805 | None | None | N |
| I/W | 0.7136 | likely_pathogenic | 0.7284 | pathogenic | -0.529 | Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| I/Y | 0.3846 | ambiguous | 0.3971 | ambiguous | -0.26 | Destabilizing | 0.991 | D | 0.798 | 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.