Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21892 | 65899;65900;65901 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| N2AB | 20251 | 60976;60977;60978 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| N2A | 19324 | 58195;58196;58197 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| N2B | 12827 | 38704;38705;38706 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| Novex-1 | 12952 | 39079;39080;39081 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| Novex-2 | 13019 | 39280;39281;39282 | chr2:178583129;178583128;178583127 | chr2:179447856;179447855;179447854 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | None | None | 0.007 | N | 0.247 | 0.099 | 0.316494231283 | gnomAD-4.0.0 | 6.84916E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00056E-07 | 0 | 0 |
| M/V | None | None | 0.003 | N | 0.157 | 0.145 | 0.305410167561 | gnomAD-4.0.0 | 4.784E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.59077E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3499 | ambiguous | 0.3222 | benign | -1.2 | Destabilizing | None | N | 0.147 | neutral | None | None | None | None | N |
| M/C | 0.7859 | likely_pathogenic | 0.7464 | pathogenic | -0.658 | Destabilizing | 0.245 | N | 0.439 | neutral | None | None | None | None | N |
| M/D | 0.8397 | likely_pathogenic | 0.8101 | pathogenic | -0.283 | Destabilizing | 0.009 | N | 0.493 | neutral | None | None | None | None | N |
| M/E | 0.5165 | ambiguous | 0.4755 | ambiguous | -0.322 | Destabilizing | None | N | 0.168 | neutral | None | None | None | None | N |
| M/F | 0.3916 | ambiguous | 0.3608 | ambiguous | -0.664 | Destabilizing | 0.044 | N | 0.309 | neutral | None | None | None | None | N |
| M/G | 0.7417 | likely_pathogenic | 0.6941 | pathogenic | -1.422 | Destabilizing | 0.009 | N | 0.445 | neutral | None | None | None | None | N |
| M/H | 0.6155 | likely_pathogenic | 0.5709 | pathogenic | -0.598 | Destabilizing | 0.245 | N | 0.517 | neutral | None | None | None | None | N |
| M/I | 0.3541 | ambiguous | 0.3249 | benign | -0.677 | Destabilizing | 0.007 | N | 0.247 | neutral | N | 0.463986248 | None | None | N |
| M/K | 0.2246 | likely_benign | 0.2125 | benign | -0.158 | Destabilizing | None | N | 0.147 | neutral | N | 0.426715939 | None | None | N |
| M/L | 0.1121 | likely_benign | 0.1019 | benign | -0.677 | Destabilizing | None | N | 0.087 | neutral | N | 0.435548853 | None | None | N |
| M/N | 0.5683 | likely_pathogenic | 0.5449 | ambiguous | 0.092 | Stabilizing | 0.044 | N | 0.513 | neutral | None | None | None | None | N |
| M/P | 0.4706 | ambiguous | 0.4142 | ambiguous | -0.824 | Destabilizing | 0.085 | N | 0.557 | neutral | None | None | None | None | N |
| M/Q | 0.2896 | likely_benign | 0.2643 | benign | -0.097 | Destabilizing | 0.022 | N | 0.285 | neutral | None | None | None | None | N |
| M/R | 0.2565 | likely_benign | 0.2322 | benign | 0.393 | Stabilizing | 0.007 | N | 0.436 | neutral | N | 0.448574078 | None | None | N |
| M/S | 0.452 | ambiguous | 0.4296 | ambiguous | -0.394 | Destabilizing | 0.004 | N | 0.337 | neutral | None | None | None | None | N |
| M/T | 0.2975 | likely_benign | 0.2733 | benign | -0.337 | Destabilizing | None | N | 0.147 | neutral | N | 0.430025603 | None | None | N |
| M/V | 0.0845 | likely_benign | 0.0847 | benign | -0.824 | Destabilizing | 0.003 | N | 0.157 | neutral | N | 0.453961255 | None | None | N |
| M/W | 0.7567 | likely_pathogenic | 0.7018 | pathogenic | -0.581 | Destabilizing | 0.788 | D | 0.432 | neutral | None | None | None | None | N |
| M/Y | 0.6195 | likely_pathogenic | 0.5864 | pathogenic | -0.537 | Destabilizing | 0.085 | N | 0.472 | neutral | 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.