Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8495 | 25708;25709;25710 | chr2:178717251;178717250;178717249 | chr2:179581978;179581977;179581976 |
| N2AB | 8178 | 24757;24758;24759 | chr2:178717251;178717250;178717249 | chr2:179581978;179581977;179581976 |
| N2A | 7251 | 21976;21977;21978 | chr2:178717251;178717250;178717249 | chr2:179581978;179581977;179581976 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | rs747674081  |
-1.169 | 1.0 | N | 0.667 | 0.598 | 0.51520462741 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| E/G | rs747674081 |
-1.169 | 1.0 | N | 0.667 | 0.598 | 0.51520462741 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/G | rs747674081 |
-1.169 | 1.0 | N | 0.667 | 0.598 | 0.51520462741 | gnomAD-4.0.0 | 6.5703E-06 | None | None | None | None | N | None | 2.4115E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| E/V | rs747674081 |
0.09 | 0.999 | D | 0.733 | 0.555 | 0.566047931302 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22792E-04 | None | 0 | None | 0 | 0 | 0 |
| E/V | rs747674081 |
0.09 | 0.999 | D | 0.733 | 0.555 | 0.566047931302 | gnomAD-4.0.0 | 6.36626E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.10932E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3785 | ambiguous | 0.291 | benign | -0.394 | Destabilizing | 0.996 | D | 0.63 | neutral | D | 0.536214493 | None | None | N |
| E/C | 0.9779 | likely_pathogenic | 0.9634 | pathogenic | -0.159 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| E/D | 0.2052 | likely_benign | 0.1518 | benign | -0.452 | Destabilizing | 0.042 | N | 0.265 | neutral | D | 0.530499242 | None | None | N |
| E/F | 0.9304 | likely_pathogenic | 0.8966 | pathogenic | -0.18 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| E/G | 0.5118 | ambiguous | 0.4244 | ambiguous | -0.622 | Destabilizing | 1.0 | D | 0.667 | neutral | N | 0.512118831 | None | None | N |
| E/H | 0.8562 | likely_pathogenic | 0.7878 | pathogenic | -0.022 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/I | 0.6208 | likely_pathogenic | 0.5218 | ambiguous | 0.181 | Stabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | N |
| E/K | 0.5503 | ambiguous | 0.4577 | ambiguous | 0.128 | Stabilizing | 0.998 | D | 0.573 | neutral | D | 0.530325883 | None | None | N |
| E/L | 0.6729 | likely_pathogenic | 0.5764 | pathogenic | 0.181 | Stabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| E/M | 0.7353 | likely_pathogenic | 0.6503 | pathogenic | 0.225 | Stabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/N | 0.5905 | likely_pathogenic | 0.459 | ambiguous | -0.196 | Destabilizing | 0.995 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/P | 0.6614 | likely_pathogenic | 0.5489 | ambiguous | 0.01 | Stabilizing | 0.998 | D | 0.735 | prob.delet. | None | None | None | None | N |
| E/Q | 0.3765 | ambiguous | 0.3037 | benign | -0.144 | Destabilizing | 0.999 | D | 0.629 | neutral | N | 0.483263701 | None | None | N |
| E/R | 0.7136 | likely_pathogenic | 0.6287 | pathogenic | 0.382 | Stabilizing | 0.999 | D | 0.715 | prob.delet. | None | None | None | None | N |
| E/S | 0.5794 | likely_pathogenic | 0.4472 | ambiguous | -0.371 | Destabilizing | 0.993 | D | 0.607 | neutral | None | None | None | None | N |
| E/T | 0.5723 | likely_pathogenic | 0.4568 | ambiguous | -0.189 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| E/V | 0.4037 | ambiguous | 0.3247 | benign | 0.01 | Stabilizing | 0.999 | D | 0.733 | prob.delet. | D | 0.532867543 | None | None | N |
| E/W | 0.9812 | likely_pathogenic | 0.9701 | pathogenic | -0.018 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| E/Y | 0.8874 | likely_pathogenic | 0.8413 | pathogenic | 0.058 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | 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.