Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18054 | 54385;54386;54387 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| N2AB | 16413 | 49462;49463;49464 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| N2A | 15486 | 46681;46682;46683 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| N2B | 8989 | 27190;27191;27192 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| Novex-1 | 9114 | 27565;27566;27567 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| Novex-2 | 9181 | 27766;27767;27768 | chr2:178605017;178605016;178605015 | chr2:179469744;179469743;179469742 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs200968679  |
-0.555 | 0.005 | N | 0.153 | 0.181 | None | gnomAD-2.1.1 | 1.39062E-04 | None | None | None | None | N | None | 4.15E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.95669E-04 | 0 |
| V/L | rs200968679 |
-0.555 | 0.005 | N | 0.153 | 0.181 | None | gnomAD-3.1.2 | 1.25021E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.6494E-04 | 0 | 0 |
| V/L | rs200968679 |
-0.555 | 0.005 | N | 0.153 | 0.181 | None | gnomAD-4.0.0 | 2.30265E-04 | None | None | None | None | N | None | 4.02868E-05 | 0 | None | 0 | 0 | None | 3.14594E-05 | 0 | 2.94936E-04 | 1.11595E-05 | 2.74344E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1461 | likely_benign | 0.1662 | benign | -0.422 | Destabilizing | 0.002 | N | 0.16 | neutral | N | 0.394683665 | None | None | N |
| V/C | 0.691 | likely_pathogenic | 0.7177 | pathogenic | -0.757 | Destabilizing | 0.974 | D | 0.648 | neutral | None | None | None | None | N |
| V/D | 0.4938 | ambiguous | 0.5642 | pathogenic | 0.193 | Stabilizing | 0.974 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/E | 0.4513 | ambiguous | 0.4946 | ambiguous | 0.108 | Stabilizing | 0.801 | D | 0.697 | prob.neutral | N | 0.471587011 | None | None | N |
| V/F | 0.2908 | likely_benign | 0.2999 | benign | -0.52 | Destabilizing | 0.949 | D | 0.697 | prob.neutral | None | None | None | None | N |
| V/G | 0.2793 | likely_benign | 0.3362 | benign | -0.566 | Destabilizing | 0.454 | N | 0.669 | neutral | N | 0.484364307 | None | None | N |
| V/H | 0.6767 | likely_pathogenic | 0.7134 | pathogenic | -0.08 | Destabilizing | 0.998 | D | 0.671 | neutral | None | None | None | None | N |
| V/I | 0.0919 | likely_benign | 0.091 | benign | -0.186 | Destabilizing | 0.525 | D | 0.503 | neutral | None | None | None | None | N |
| V/K | 0.5624 | ambiguous | 0.5983 | pathogenic | -0.293 | Destabilizing | 0.842 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/L | 0.2949 | likely_benign | 0.2956 | benign | -0.186 | Destabilizing | 0.005 | N | 0.153 | neutral | N | 0.4585245 | None | None | N |
| V/M | 0.2064 | likely_benign | 0.1957 | benign | -0.418 | Destabilizing | 0.934 | D | 0.644 | neutral | N | 0.503296785 | None | None | N |
| V/N | 0.3337 | likely_benign | 0.3689 | ambiguous | -0.138 | Destabilizing | 0.974 | D | 0.715 | prob.delet. | None | None | None | None | N |
| V/P | 0.9437 | likely_pathogenic | 0.9637 | pathogenic | -0.23 | Destabilizing | 0.974 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/Q | 0.4386 | ambiguous | 0.4669 | ambiguous | -0.291 | Destabilizing | 0.974 | D | 0.683 | prob.neutral | None | None | None | None | N |
| V/R | 0.5278 | ambiguous | 0.5849 | pathogenic | 0.109 | Stabilizing | 0.974 | D | 0.733 | prob.delet. | None | None | None | None | N |
| V/S | 0.2049 | likely_benign | 0.2319 | benign | -0.584 | Destabilizing | 0.525 | D | 0.643 | neutral | None | None | None | None | N |
| V/T | 0.1661 | likely_benign | 0.1754 | benign | -0.554 | Destabilizing | 0.688 | D | 0.516 | neutral | None | None | None | None | N |
| V/W | 0.928 | likely_pathogenic | 0.9359 | pathogenic | -0.596 | Destabilizing | 0.998 | D | 0.681 | prob.neutral | None | None | None | None | N |
| V/Y | 0.6677 | likely_pathogenic | 0.7007 | pathogenic | -0.3 | Destabilizing | 0.991 | D | 0.685 | prob.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.