Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31769 | 95530;95531;95532 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| N2AB | 30128 | 90607;90608;90609 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| N2A | 29201 | 87826;87827;87828 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| N2B | 22704 | 68335;68336;68337 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| Novex-1 | 22829 | 68710;68711;68712 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| Novex-2 | 22896 | 68911;68912;68913 | chr2:178545931;178545930;178545929 | chr2:179410658;179410657;179410656 |
| 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/F | None | None | 0.998 | N | 0.814 | 0.438 | 0.811294113689 | gnomAD-4.0.0 | 6.84196E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9946E-07 | 0 | 0 |
| V/I | rs374445709  |
-0.089 | 0.982 | N | 0.609 | 0.212 | None | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 4.13E-05 | 2.83E-05 | None | 0 | 2.05065E-04 | None | 9.8E-05 | None | 0 | 3.13E-05 | 0 |
| V/I | rs374445709 |
-0.089 | 0.982 | N | 0.609 | 0.212 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 9.65E-05 | 6.55E-05 | 0 | 0 | 1.93125E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs374445709 |
-0.089 | 0.982 | N | 0.609 | 0.212 | None | gnomAD-4.0.0 | 1.73513E-05 | None | None | None | None | N | None | 6.67468E-05 | 1.66717E-05 | None | 0 | 8.91544E-05 | None | 0 | 0 | 1.27141E-05 | 2.19578E-05 | 1.60113E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.294 | likely_benign | 0.3312 | benign | -1.661 | Destabilizing | 0.061 | N | 0.331 | neutral | D | 0.52397034 | None | None | N |
| V/C | 0.8055 | likely_pathogenic | 0.8313 | pathogenic | -1.148 | Destabilizing | 0.999 | D | 0.81 | deleterious | None | None | None | None | N |
| V/D | 0.9516 | likely_pathogenic | 0.972 | pathogenic | -2.24 | Highly Destabilizing | 0.92 | D | 0.789 | deleterious | N | 0.511903524 | None | None | N |
| V/E | 0.9036 | likely_pathogenic | 0.9376 | pathogenic | -1.989 | Destabilizing | 0.939 | D | 0.781 | deleterious | None | None | None | None | N |
| V/F | 0.5945 | likely_pathogenic | 0.6224 | pathogenic | -0.944 | Destabilizing | 0.998 | D | 0.814 | deleterious | N | 0.50886165 | None | None | N |
| V/G | 0.6327 | likely_pathogenic | 0.6949 | pathogenic | -2.218 | Highly Destabilizing | 0.826 | D | 0.768 | deleterious | D | 0.557266294 | None | None | N |
| V/H | 0.9617 | likely_pathogenic | 0.9716 | pathogenic | -2.061 | Highly Destabilizing | 0.999 | D | 0.855 | deleterious | None | None | None | None | N |
| V/I | 0.0903 | likely_benign | 0.0905 | benign | -0.105 | Destabilizing | 0.982 | D | 0.609 | neutral | N | 0.499762542 | None | None | N |
| V/K | 0.9535 | likely_pathogenic | 0.9675 | pathogenic | -1.372 | Destabilizing | 0.939 | D | 0.78 | deleterious | None | None | None | None | N |
| V/L | 0.4005 | ambiguous | 0.4574 | ambiguous | -0.105 | Destabilizing | 0.924 | D | 0.668 | neutral | N | 0.477899243 | None | None | N |
| V/M | 0.3734 | ambiguous | 0.4098 | ambiguous | -0.179 | Destabilizing | 0.997 | D | 0.659 | neutral | None | None | None | None | N |
| V/N | 0.8544 | likely_pathogenic | 0.8918 | pathogenic | -1.774 | Destabilizing | 0.982 | D | 0.803 | deleterious | None | None | None | None | N |
| V/P | 0.9219 | likely_pathogenic | 0.9353 | pathogenic | -0.596 | Destabilizing | 0.991 | D | 0.806 | deleterious | None | None | None | None | N |
| V/Q | 0.8983 | likely_pathogenic | 0.9254 | pathogenic | -1.541 | Destabilizing | 0.991 | D | 0.828 | deleterious | None | None | None | None | N |
| V/R | 0.9425 | likely_pathogenic | 0.9604 | pathogenic | -1.396 | Destabilizing | 0.991 | D | 0.835 | deleterious | None | None | None | None | N |
| V/S | 0.5577 | ambiguous | 0.6025 | pathogenic | -2.376 | Highly Destabilizing | 0.2 | N | 0.527 | neutral | None | None | None | None | N |
| V/T | 0.459 | ambiguous | 0.4783 | ambiguous | -1.963 | Destabilizing | 0.759 | D | 0.655 | neutral | None | None | None | None | N |
| V/W | 0.9873 | likely_pathogenic | 0.9901 | pathogenic | -1.489 | Destabilizing | 0.999 | D | 0.83 | deleterious | None | None | None | None | N |
| V/Y | 0.939 | likely_pathogenic | 0.9508 | pathogenic | -1.017 | Destabilizing | 0.997 | D | 0.811 | 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.