Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1474 | 4645;4646;4647 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| N2AB | 1474 | 4645;4646;4647 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| N2A | 1474 | 4645;4646;4647 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| N2B | 1428 | 4507;4508;4509 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| Novex-1 | 1428 | 4507;4508;4509 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| Novex-2 | 1428 | 4507;4508;4509 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
| Novex-3 | 1474 | 4645;4646;4647 | chr2:178777764;178777763;178777762 | chr2:179642491;179642490;179642489 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | rs367739896  |
-1.304 | 1.0 | D | 0.557 | 0.569 | 0.661867001231 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 6.53E-05 | None | 0 | 0 | 0 |
| A/G | rs367739896 |
-1.304 | 1.0 | D | 0.557 | 0.569 | 0.661867001231 | gnomAD-4.0.0 | 4.78878E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.11519E-05 | 0 |
| A/T | None | None | 1.0 | D | 0.683 | 0.573 | 0.608471955132 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| A/V | rs367739896 |
0.109 | 1.0 | N | 0.589 | 0.501 | None | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7472 | likely_pathogenic | 0.7573 | pathogenic | -0.472 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| A/D | 0.9965 | likely_pathogenic | 0.997 | pathogenic | -1.494 | Destabilizing | 1.0 | D | 0.837 | deleterious | D | 0.751148561 | None | None | N |
| A/E | 0.99 | likely_pathogenic | 0.9913 | pathogenic | -1.279 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| A/F | 0.9552 | likely_pathogenic | 0.9602 | pathogenic | -0.396 | Destabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/G | 0.4487 | ambiguous | 0.4592 | ambiguous | -1.13 | Destabilizing | 1.0 | D | 0.557 | neutral | D | 0.670060426 | None | None | N |
| A/H | 0.9929 | likely_pathogenic | 0.9941 | pathogenic | -1.518 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| A/I | 0.7308 | likely_pathogenic | 0.7534 | pathogenic | 0.652 | Stabilizing | 1.0 | D | 0.845 | deleterious | None | None | None | None | N |
| A/K | 0.9954 | likely_pathogenic | 0.9961 | pathogenic | -0.748 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/L | 0.7081 | likely_pathogenic | 0.7262 | pathogenic | 0.652 | Stabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | N |
| A/M | 0.8042 | likely_pathogenic | 0.8229 | pathogenic | 0.443 | Stabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| A/N | 0.9847 | likely_pathogenic | 0.987 | pathogenic | -1.045 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | N |
| A/P | 0.9854 | likely_pathogenic | 0.985 | pathogenic | 0.265 | Stabilizing | 1.0 | D | 0.839 | deleterious | D | 0.751279833 | None | None | N |
| A/Q | 0.9777 | likely_pathogenic | 0.9803 | pathogenic | -0.805 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| A/R | 0.9869 | likely_pathogenic | 0.9884 | pathogenic | -0.979 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | N |
| A/S | 0.3425 | ambiguous | 0.3616 | ambiguous | -1.496 | Destabilizing | 1.0 | D | 0.577 | neutral | D | 0.751835609 | None | None | N |
| A/T | 0.3841 | ambiguous | 0.4201 | ambiguous | -1.132 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | D | 0.545689969 | None | None | N |
| A/V | 0.3605 | ambiguous | 0.3837 | ambiguous | 0.265 | Stabilizing | 1.0 | D | 0.589 | neutral | N | 0.517598212 | None | None | N |
| A/W | 0.9978 | likely_pathogenic | 0.9982 | pathogenic | -1.141 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| A/Y | 0.9897 | likely_pathogenic | 0.9911 | pathogenic | -0.474 | Destabilizing | 1.0 | D | 0.857 | 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.