Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19236 | 57931;57932;57933 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| N2AB | 17595 | 53008;53009;53010 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| N2A | 16668 | 50227;50228;50229 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| N2B | 10171 | 30736;30737;30738 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| Novex-1 | 10296 | 31111;31112;31113 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| Novex-2 | 10363 | 31312;31313;31314 | chr2:178595648;178595647;178595646 | chr2:179460375;179460374;179460373 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/H | rs375797796  |
0.517 | 0.859 | N | 0.545 | 0.318 | 0.359557344763 | gnomAD-2.1.1 | 8.35E-06 | None | None | None | None | N | None | 6.78E-05 | 2.98E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/H | rs375797796 |
0.517 | 0.859 | N | 0.545 | 0.318 | 0.359557344763 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 1.20773E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| Y/H | rs375797796 |
0.517 | 0.859 | N | 0.545 | 0.318 | 0.359557344763 | gnomAD-4.0.0 | 4.35479E-06 | None | None | None | None | N | None | 6.68235E-05 | 1.68862E-05 | None | 0 | 0 | None | 0 | 0 | 8.49681E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.3589 | ambiguous | 0.4505 | ambiguous | -1.034 | Destabilizing | 0.005 | N | 0.307 | neutral | None | None | None | None | N |
| Y/C | 0.0971 | likely_benign | 0.1429 | benign | 0.016 | Stabilizing | 0.002 | N | 0.423 | neutral | N | 0.471102068 | None | None | N |
| Y/D | 0.4332 | ambiguous | 0.512 | ambiguous | 0.682 | Stabilizing | 0.667 | D | 0.634 | neutral | N | 0.424299204 | None | None | N |
| Y/E | 0.7697 | likely_pathogenic | 0.8167 | pathogenic | 0.684 | Stabilizing | 0.726 | D | 0.585 | neutral | None | None | None | None | N |
| Y/F | 0.1067 | likely_benign | 0.124 | benign | -0.507 | Destabilizing | 0.364 | N | 0.509 | neutral | N | 0.456046263 | None | None | N |
| Y/G | 0.3262 | likely_benign | 0.4265 | ambiguous | -1.265 | Destabilizing | 0.272 | N | 0.531 | neutral | None | None | None | None | N |
| Y/H | 0.2917 | likely_benign | 0.3801 | ambiguous | -0.099 | Destabilizing | 0.859 | D | 0.545 | neutral | N | 0.481635354 | None | None | N |
| Y/I | 0.5333 | ambiguous | 0.6341 | pathogenic | -0.415 | Destabilizing | 0.567 | D | 0.529 | neutral | None | None | None | None | N |
| Y/K | 0.7416 | likely_pathogenic | 0.8129 | pathogenic | 0.026 | Stabilizing | 0.726 | D | 0.553 | neutral | None | None | None | None | N |
| Y/L | 0.4202 | ambiguous | 0.5039 | ambiguous | -0.415 | Destabilizing | 0.157 | N | 0.549 | neutral | None | None | None | None | N |
| Y/M | 0.5294 | ambiguous | 0.5993 | pathogenic | -0.192 | Destabilizing | 0.968 | D | 0.585 | neutral | None | None | None | None | N |
| Y/N | 0.2139 | likely_benign | 0.2761 | benign | -0.099 | Destabilizing | 0.667 | D | 0.614 | neutral | N | 0.463990956 | None | None | N |
| Y/P | 0.7121 | likely_pathogenic | 0.8386 | pathogenic | -0.604 | Destabilizing | 0.726 | D | 0.631 | neutral | None | None | None | None | N |
| Y/Q | 0.6264 | likely_pathogenic | 0.7237 | pathogenic | -0.073 | Destabilizing | 0.89 | D | 0.576 | neutral | None | None | None | None | N |
| Y/R | 0.5793 | likely_pathogenic | 0.6884 | pathogenic | 0.325 | Stabilizing | 0.726 | D | 0.615 | neutral | None | None | None | None | N |
| Y/S | 0.1726 | likely_benign | 0.23 | benign | -0.59 | Destabilizing | 0.124 | N | 0.504 | neutral | N | 0.422048333 | None | None | N |
| Y/T | 0.3361 | likely_benign | 0.3969 | ambiguous | -0.491 | Destabilizing | 0.567 | D | 0.499 | neutral | None | None | None | None | N |
| Y/V | 0.3356 | likely_benign | 0.4111 | ambiguous | -0.604 | Destabilizing | 0.157 | N | 0.519 | neutral | None | None | None | None | N |
| Y/W | 0.4062 | ambiguous | 0.4583 | ambiguous | -0.498 | Destabilizing | 0.968 | D | 0.541 | 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.