Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26091 | 78496;78497;78498 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| N2AB | 24450 | 73573;73574;73575 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| N2A | 23523 | 70792;70793;70794 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| N2B | 17026 | 51301;51302;51303 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| Novex-1 | 17151 | 51676;51677;51678 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| Novex-2 | 17218 | 51877;51878;51879 | chr2:178567861;178567860;178567859 | chr2:179432588;179432587;179432586 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/S | None | None | 1.0 | N | 0.872 | 0.481 | 0.39709148275 | gnomAD-4.0.0 | 6.84317E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99588E-07 | 0 | 0 |
| P/T | rs1706513833  |
None | 1.0 | N | 0.865 | 0.498 | 0.458283960492 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/T | rs1706513833 |
None | 1.0 | N | 0.865 | 0.498 | 0.458283960492 | gnomAD-4.0.0 | 1.23973E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69552E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0782 | likely_benign | 0.0856 | benign | -1.333 | Destabilizing | 1.0 | D | 0.847 | deleterious | N | 0.487403746 | None | None | N |
| P/C | 0.543 | ambiguous | 0.5587 | ambiguous | -1.089 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| P/D | 0.8834 | likely_pathogenic | 0.8903 | pathogenic | -1.7 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| P/E | 0.549 | ambiguous | 0.5795 | pathogenic | -1.76 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/F | 0.719 | likely_pathogenic | 0.7358 | pathogenic | -1.418 | Destabilizing | 1.0 | D | 0.921 | deleterious | None | None | None | None | N |
| P/G | 0.5822 | likely_pathogenic | 0.6329 | pathogenic | -1.567 | Destabilizing | 1.0 | D | 0.907 | deleterious | None | None | None | None | N |
| P/H | 0.4347 | ambiguous | 0.4444 | ambiguous | -1.065 | Destabilizing | 1.0 | D | 0.899 | deleterious | None | None | None | None | N |
| P/I | 0.4386 | ambiguous | 0.4143 | ambiguous | -0.806 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| P/K | 0.521 | ambiguous | 0.4988 | ambiguous | -0.992 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/L | 0.2561 | likely_benign | 0.2544 | benign | -0.806 | Destabilizing | 1.0 | D | 0.905 | deleterious | D | 0.5471833 | None | None | N |
| P/M | 0.4646 | ambiguous | 0.4762 | ambiguous | -0.54 | Destabilizing | 1.0 | D | 0.896 | deleterious | None | None | None | None | N |
| P/N | 0.7207 | likely_pathogenic | 0.7261 | pathogenic | -0.829 | Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| P/Q | 0.3096 | likely_benign | 0.3293 | benign | -1.153 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.527304619 | None | None | N |
| P/R | 0.3428 | ambiguous | 0.3363 | benign | -0.391 | Destabilizing | 1.0 | D | 0.916 | deleterious | N | 0.511682352 | None | None | N |
| P/S | 0.1923 | likely_benign | 0.2176 | benign | -1.247 | Destabilizing | 1.0 | D | 0.872 | deleterious | N | 0.505655191 | None | None | N |
| P/T | 0.2253 | likely_benign | 0.223 | benign | -1.211 | Destabilizing | 1.0 | D | 0.865 | deleterious | N | 0.514582415 | None | None | N |
| P/V | 0.3145 | likely_benign | 0.3003 | benign | -0.949 | Destabilizing | 1.0 | D | 0.906 | deleterious | None | None | None | None | N |
| P/W | 0.9012 | likely_pathogenic | 0.9121 | pathogenic | -1.522 | Destabilizing | 1.0 | D | 0.888 | deleterious | None | None | None | None | N |
| P/Y | 0.7402 | likely_pathogenic | 0.7455 | pathogenic | -1.206 | Destabilizing | 1.0 | D | 0.928 | 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.