Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31690 | 95293;95294;95295 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| N2AB | 30049 | 90370;90371;90372 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| N2A | 29122 | 87589;87590;87591 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| N2B | 22625 | 68098;68099;68100 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| Novex-1 | 22750 | 68473;68474;68475 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| Novex-2 | 22817 | 68674;68675;68676 | chr2:178546263;178546262;178546261 | chr2:179410990;179410989;179410988 |
| 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/A | rs1224358849  |
None | 0.17 | N | 0.369 | 0.251 | 0.445308138417 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs1224358849 |
None | 0.17 | N | 0.369 | 0.251 | 0.445308138417 | gnomAD-4.0.0 | 2.02981E-06 | None | None | None | None | N | None | 1.74715E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20491E-06 | 0 | 0 |
| V/L | rs727503543 |
None | 0.046 | N | 0.353 | 0.359 | 0.455996456696 | gnomAD-4.0.0 | 6.84294E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99594E-07 | 0 | 0 |
| V/M | rs727503543 |
-0.757 | 0.982 | N | 0.753 | 0.522 | 0.653474937825 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| V/M | rs727503543 |
-0.757 | 0.982 | N | 0.753 | 0.522 | 0.653474937825 | gnomAD-3.1.2 | 3.28E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| V/M | rs727503543 |
-0.757 | 0.982 | N | 0.753 | 0.522 | 0.653474937825 | gnomAD-4.0.0 | 4.64806E-05 | None | None | None | None | N | None | 1.33469E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 6.10351E-05 | 0 | 3.20205E-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 | 0.3786 | ambiguous | 0.3563 | ambiguous | -1.74 | Destabilizing | 0.17 | N | 0.369 | neutral | N | 0.393771227 | None | None | N |
| V/C | 0.9161 | likely_pathogenic | 0.9071 | pathogenic | -1.312 | Destabilizing | 0.999 | D | 0.769 | deleterious | None | None | None | None | N |
| V/D | 0.9983 | likely_pathogenic | 0.9981 | pathogenic | -2.02 | Highly Destabilizing | 0.998 | D | 0.863 | deleterious | None | None | None | None | N |
| V/E | 0.9928 | likely_pathogenic | 0.9925 | pathogenic | -1.943 | Destabilizing | 0.991 | D | 0.834 | deleterious | D | 0.522241505 | None | None | N |
| V/F | 0.9123 | likely_pathogenic | 0.9016 | pathogenic | -1.176 | Destabilizing | 0.986 | D | 0.812 | deleterious | None | None | None | None | N |
| V/G | 0.8098 | likely_pathogenic | 0.7915 | pathogenic | -2.146 | Highly Destabilizing | 0.982 | D | 0.813 | deleterious | D | 0.533238476 | None | None | N |
| V/H | 0.9988 | likely_pathogenic | 0.9987 | pathogenic | -1.857 | Destabilizing | 0.999 | D | 0.834 | deleterious | None | None | None | None | N |
| V/I | 0.1385 | likely_benign | 0.1361 | benign | -0.686 | Destabilizing | 0.807 | D | 0.637 | neutral | None | None | None | None | N |
| V/K | 0.9971 | likely_pathogenic | 0.9966 | pathogenic | -1.628 | Destabilizing | 0.993 | D | 0.835 | deleterious | None | None | None | None | N |
| V/L | 0.3979 | ambiguous | 0.3729 | ambiguous | -0.686 | Destabilizing | 0.046 | N | 0.353 | neutral | N | 0.44429134 | None | None | N |
| V/M | 0.5968 | likely_pathogenic | 0.5833 | pathogenic | -0.604 | Destabilizing | 0.982 | D | 0.753 | deleterious | N | 0.495489969 | None | None | N |
| V/N | 0.9927 | likely_pathogenic | 0.9919 | pathogenic | -1.57 | Destabilizing | 0.998 | D | 0.849 | deleterious | None | None | None | None | N |
| V/P | 0.9976 | likely_pathogenic | 0.9965 | pathogenic | -1.004 | Destabilizing | 0.998 | D | 0.845 | deleterious | None | None | None | None | N |
| V/Q | 0.9908 | likely_pathogenic | 0.9899 | pathogenic | -1.628 | Destabilizing | 0.998 | D | 0.827 | deleterious | None | None | None | None | N |
| V/R | 0.9921 | likely_pathogenic | 0.9913 | pathogenic | -1.214 | Destabilizing | 0.993 | D | 0.859 | deleterious | None | None | None | None | N |
| V/S | 0.889 | likely_pathogenic | 0.8848 | pathogenic | -2.102 | Highly Destabilizing | 0.973 | D | 0.811 | deleterious | None | None | None | None | N |
| V/T | 0.7963 | likely_pathogenic | 0.779 | pathogenic | -1.909 | Destabilizing | 0.953 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/W | 0.9993 | likely_pathogenic | 0.9992 | pathogenic | -1.537 | Destabilizing | 0.999 | D | 0.817 | deleterious | None | None | None | None | N |
| V/Y | 0.9955 | likely_pathogenic | 0.9946 | pathogenic | -1.207 | Destabilizing | 0.993 | D | 0.798 | 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.