Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 946 | 3061;3062;3063 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| N2AB | 946 | 3061;3062;3063 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| N2A | 946 | 3061;3062;3063 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| N2B | 900 | 2923;2924;2925 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| Novex-1 | 900 | 2923;2924;2925 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| Novex-2 | 900 | 2923;2924;2925 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
| Novex-3 | 946 | 3061;3062;3063 | chr2:178783725;178783724;178783723 | chr2:179648452;179648451;179648450 |
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/I | rs752246051  |
-0.081 | 0.37 | N | 0.171 | 0.178 | None | gnomAD-2.1.1 | 1.77E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.88E-05 | 0 |
| V/I | rs752246051 |
-0.081 | 0.37 | N | 0.171 | 0.178 | None | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs752246051 |
-0.081 | 0.37 | N | 0.171 | 0.178 | None | gnomAD-4.0.0 | 3.03764E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.15397E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4518 | ambiguous | 0.5562 | ambiguous | -0.602 | Destabilizing | 0.948 | D | 0.443 | neutral | D | 0.562924498 | None | None | I |
| V/C | 0.9335 | likely_pathogenic | 0.9519 | pathogenic | -0.577 | Destabilizing | 1.0 | D | 0.573 | neutral | None | None | None | None | I |
| V/D | 0.7244 | likely_pathogenic | 0.8472 | pathogenic | -0.323 | Destabilizing | 0.999 | D | 0.675 | neutral | D | 0.570333519 | None | None | I |
| V/E | 0.4883 | ambiguous | 0.6066 | pathogenic | -0.432 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| V/F | 0.3455 | ambiguous | 0.4511 | ambiguous | -0.756 | Destabilizing | 0.997 | D | 0.613 | neutral | D | 0.613547043 | None | None | I |
| V/G | 0.5618 | ambiguous | 0.7017 | pathogenic | -0.758 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | D | 0.614502016 | None | None | I |
| V/H | 0.7977 | likely_pathogenic | 0.8698 | pathogenic | -0.287 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| V/I | 0.0962 | likely_benign | 0.0931 | benign | -0.339 | Destabilizing | 0.37 | N | 0.171 | neutral | N | 0.474879375 | None | None | I |
| V/K | 0.5764 | likely_pathogenic | 0.6696 | pathogenic | -0.497 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | I |
| V/L | 0.303 | likely_benign | 0.3497 | ambiguous | -0.339 | Destabilizing | 0.9 | D | 0.321 | neutral | N | 0.488714436 | None | None | I |
| V/M | 0.2822 | likely_benign | 0.3293 | benign | -0.3 | Destabilizing | 0.998 | D | 0.547 | neutral | None | None | None | None | I |
| V/N | 0.6436 | likely_pathogenic | 0.7426 | pathogenic | -0.21 | Destabilizing | 0.999 | D | 0.685 | prob.neutral | None | None | None | None | I |
| V/P | 0.9282 | likely_pathogenic | 0.9668 | pathogenic | -0.391 | Destabilizing | 0.999 | D | 0.641 | neutral | None | None | None | None | I |
| V/Q | 0.5198 | ambiguous | 0.606 | pathogenic | -0.468 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | I |
| V/R | 0.5371 | ambiguous | 0.6566 | pathogenic | 0.058 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| V/S | 0.5416 | ambiguous | 0.6515 | pathogenic | -0.604 | Destabilizing | 0.999 | D | 0.633 | neutral | None | None | None | None | I |
| V/T | 0.4416 | ambiguous | 0.5083 | ambiguous | -0.611 | Destabilizing | 0.992 | D | 0.461 | neutral | None | None | None | None | I |
| V/W | 0.9456 | likely_pathogenic | 0.9709 | pathogenic | -0.831 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/Y | 0.8002 | likely_pathogenic | 0.8671 | pathogenic | -0.538 | Destabilizing | 0.999 | D | 0.582 | neutral | None | None | None | None | I |
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.