Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22921 | 68986;68987;68988 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| N2AB | 21280 | 64063;64064;64065 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| N2A | 20353 | 61282;61283;61284 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| N2B | 13856 | 41791;41792;41793 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| Novex-1 | 13981 | 42166;42167;42168 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| Novex-2 | 14048 | 42367;42368;42369 | chr2:178577665;178577664;178577663 | chr2:179442392;179442391;179442390 |
| 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 | rs534567766  |
-0.033 | 0.004 | N | 0.263 | 0.253 | 0.243398259712 | gnomAD-2.1.1 | 1.93436E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.56996E-03 | None | 0 | 7.85E-06 | 7.05617E-04 |
| T/I | rs534567766 |
-0.033 | 0.004 | N | 0.263 | 0.253 | 0.243398259712 | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.06954E-03 | 0 |
| T/I | rs534567766 |
-0.033 | 0.004 | N | 0.263 | 0.253 | 0.243398259712 | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 2E-03 | None |
| T/I | rs534567766 |
-0.033 | 0.004 | N | 0.263 | 0.253 | 0.243398259712 | gnomAD-4.0.0 | 9.73206E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 4.95868E-04 | 1.69559E-06 | 1.59274E-03 | 1.12072E-04 |
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 | 0.0798 | likely_benign | 0.0804 | benign | -0.669 | Destabilizing | 0.007 | N | 0.055 | neutral | N | 0.341491394 | None | None | I |
| T/C | 0.536 | ambiguous | 0.5773 | pathogenic | -0.262 | Destabilizing | 0.992 | D | 0.342 | neutral | None | None | None | None | I |
| T/D | 0.6517 | likely_pathogenic | 0.6783 | pathogenic | -0.533 | Destabilizing | 0.617 | D | 0.387 | neutral | None | None | None | None | I |
| T/E | 0.4859 | ambiguous | 0.5296 | ambiguous | -0.577 | Destabilizing | 0.617 | D | 0.335 | neutral | None | None | None | None | I |
| T/F | 0.4358 | ambiguous | 0.4851 | ambiguous | -0.935 | Destabilizing | 0.85 | D | 0.478 | neutral | None | None | None | None | I |
| T/G | 0.3289 | likely_benign | 0.3341 | benign | -0.876 | Destabilizing | 0.25 | N | 0.438 | neutral | None | None | None | None | I |
| T/H | 0.4372 | ambiguous | 0.4727 | ambiguous | -1.218 | Destabilizing | 0.992 | D | 0.433 | neutral | None | None | None | None | I |
| T/I | 0.2751 | likely_benign | 0.3166 | benign | -0.218 | Destabilizing | 0.004 | N | 0.263 | neutral | N | 0.434249626 | None | None | I |
| T/K | 0.3886 | ambiguous | 0.4359 | ambiguous | -0.714 | Destabilizing | 0.549 | D | 0.347 | neutral | N | 0.439519373 | None | None | I |
| T/L | 0.1491 | likely_benign | 0.1644 | benign | -0.218 | Destabilizing | 0.103 | N | 0.383 | neutral | None | None | None | None | I |
| T/M | 0.1065 | likely_benign | 0.1138 | benign | 0.282 | Stabilizing | 0.85 | D | 0.346 | neutral | None | None | None | None | I |
| T/N | 0.2125 | likely_benign | 0.2303 | benign | -0.559 | Destabilizing | 0.617 | D | 0.255 | neutral | None | None | None | None | I |
| T/P | 0.4094 | ambiguous | 0.4088 | ambiguous | -0.338 | Destabilizing | 0.896 | D | 0.359 | neutral | N | 0.463167024 | None | None | I |
| T/Q | 0.3572 | ambiguous | 0.3884 | ambiguous | -0.845 | Destabilizing | 0.92 | D | 0.373 | neutral | None | None | None | None | I |
| T/R | 0.3033 | likely_benign | 0.3547 | ambiguous | -0.344 | Destabilizing | 0.896 | D | 0.373 | neutral | N | 0.456470338 | None | None | I |
| T/S | 0.1374 | likely_benign | 0.1345 | benign | -0.749 | Destabilizing | 0.02 | N | 0.056 | neutral | N | 0.400000979 | None | None | I |
| T/V | 0.1854 | likely_benign | 0.2052 | benign | -0.338 | Destabilizing | 0.103 | N | 0.265 | neutral | None | None | None | None | I |
| T/W | 0.7897 | likely_pathogenic | 0.829 | pathogenic | -0.888 | Destabilizing | 0.992 | D | 0.512 | neutral | None | None | None | None | I |
| T/Y | 0.4779 | ambiguous | 0.54 | ambiguous | -0.654 | Destabilizing | 0.92 | D | 0.461 | neutral | None | None | None | None | I |
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.