Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30046 | 90361;90362;90363 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| N2AB | 28405 | 85438;85439;85440 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| N2A | 27478 | 82657;82658;82659 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| N2B | 20981 | 63166;63167;63168 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| Novex-1 | 21106 | 63541;63542;63543 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| Novex-2 | 21173 | 63742;63743;63744 | chr2:178552764;178552763;178552762 | chr2:179417491;179417490;179417489 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs1400410632  |
-1.15 | 1.0 | N | 0.761 | 0.478 | 0.693281465932 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs1400410632 |
-1.15 | 1.0 | N | 0.761 | 0.478 | 0.693281465932 | gnomAD-4.0.0 | 6.84174E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52003E-05 | None | 0 | 0 | 0 | 0 | 0 |
| S/Y | None | None | 1.0 | N | 0.826 | 0.432 | 0.812780994167 | gnomAD-4.0.0 | 6.84174E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65634E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.111 | likely_benign | 0.1056 | benign | -0.645 | Destabilizing | 0.997 | D | 0.479 | neutral | N | 0.497535479 | None | None | N |
| S/C | 0.1711 | likely_benign | 0.1608 | benign | -0.94 | Destabilizing | 1.0 | D | 0.761 | deleterious | N | 0.495448792 | None | None | N |
| S/D | 0.6737 | likely_pathogenic | 0.6744 | pathogenic | -1.423 | Destabilizing | 0.999 | D | 0.544 | neutral | None | None | None | None | N |
| S/E | 0.7576 | likely_pathogenic | 0.7523 | pathogenic | -1.399 | Destabilizing | 0.999 | D | 0.534 | neutral | None | None | None | None | N |
| S/F | 0.4173 | ambiguous | 0.4098 | ambiguous | -1.137 | Destabilizing | 1.0 | D | 0.819 | deleterious | N | 0.499309905 | None | None | N |
| S/G | 0.1504 | likely_benign | 0.1487 | benign | -0.838 | Destabilizing | 0.999 | D | 0.487 | neutral | None | None | None | None | N |
| S/H | 0.4636 | ambiguous | 0.4618 | ambiguous | -1.351 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| S/I | 0.5269 | ambiguous | 0.4977 | ambiguous | -0.231 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| S/K | 0.7794 | likely_pathogenic | 0.777 | pathogenic | -0.557 | Destabilizing | 0.999 | D | 0.54 | neutral | None | None | None | None | N |
| S/L | 0.2496 | likely_benign | 0.2331 | benign | -0.231 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| S/M | 0.3062 | likely_benign | 0.2894 | benign | -0.002 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | N |
| S/N | 0.2726 | likely_benign | 0.2771 | benign | -0.851 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | N |
| S/P | 0.9891 | likely_pathogenic | 0.9874 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.534530911 | None | None | N |
| S/Q | 0.6655 | likely_pathogenic | 0.6625 | pathogenic | -1.123 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| S/R | 0.7234 | likely_pathogenic | 0.7202 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| S/T | 0.091 | likely_benign | 0.0871 | benign | -0.705 | Destabilizing | 0.999 | D | 0.495 | neutral | N | 0.477554665 | None | None | N |
| S/V | 0.4197 | ambiguous | 0.3952 | ambiguous | -0.34 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| S/W | 0.5869 | likely_pathogenic | 0.5844 | pathogenic | -1.192 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | N |
| S/Y | 0.3598 | ambiguous | 0.3477 | ambiguous | -0.805 | Destabilizing | 1.0 | D | 0.826 | deleterious | N | 0.494839681 | 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.