Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19959 | 60100;60101;60102 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| N2AB | 18318 | 55177;55178;55179 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| N2A | 17391 | 52396;52397;52398 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| N2B | 10894 | 32905;32906;32907 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| Novex-1 | 11019 | 33280;33281;33282 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| Novex-2 | 11086 | 33481;33482;33483 | chr2:178592029;178592028;178592027 | chr2:179456756;179456755;179456754 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs564432498  |
-0.306 | 1.0 | N | 0.774 | 0.377 | 0.581818759506 | gnomAD-2.1.1 | 1.97652E-04 | None | None | None | None | I | None | 0 | 5.82E-05 | None | 0 | 0 | None | 1.47136E-03 | None | 0 | 8.91E-06 | 1.66445E-04 |
| R/C | rs564432498 |
-0.306 | 1.0 | N | 0.774 | 0.377 | 0.581818759506 | gnomAD-3.1.2 | 6.58E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 1.86722E-03 | 0 |
| R/C | rs564432498 |
-0.306 | 1.0 | N | 0.774 | 0.377 | 0.581818759506 | 1000 genomes | 1.19808E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 6.1E-03 | None |
| R/C | rs564432498 |
-0.306 | 1.0 | N | 0.774 | 0.377 | 0.581818759506 | gnomAD-4.0.0 | 9.85676E-05 | None | None | None | None | I | None | 0 | 1.66856E-05 | None | 0 | 0 | None | 1.56333E-05 | 0 | 6.78245E-06 | 1.55975E-03 | 1.12108E-04 |
| R/H | rs748120315 |
-0.887 | 1.0 | N | 0.791 | 0.436 | 0.399159426805 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 1.78E-05 | 0 |
| R/H | rs748120315 |
-0.887 | 1.0 | N | 0.791 | 0.436 | 0.399159426805 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs748120315 |
-0.887 | 1.0 | N | 0.791 | 0.436 | 0.399159426805 | gnomAD-4.0.0 | 2.66566E-05 | None | None | None | None | I | None | 0 | 1.66872E-05 | None | 0 | 2.24024E-05 | None | 0 | 0 | 3.13687E-05 | 2.19674E-05 | 3.20297E-05 |
| R/S | rs564432498 |
None | 1.0 | N | 0.705 | 0.307 | 0.341226946553 | gnomAD-4.0.0 | 6.84504E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99656E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5828 | likely_pathogenic | 0.4466 | ambiguous | -0.751 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | I |
| R/C | 0.2112 | likely_benign | 0.1669 | benign | -0.789 | Destabilizing | 1.0 | D | 0.774 | deleterious | N | 0.476141725 | None | None | I |
| R/D | 0.8895 | likely_pathogenic | 0.8349 | pathogenic | -0.028 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/E | 0.5448 | ambiguous | 0.4429 | ambiguous | 0.116 | Stabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | I |
| R/F | 0.6534 | likely_pathogenic | 0.5585 | ambiguous | -0.51 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/G | 0.5438 | ambiguous | 0.426 | ambiguous | -1.063 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.517401366 | None | None | I |
| R/H | 0.178 | likely_benign | 0.1478 | benign | -1.379 | Destabilizing | 1.0 | D | 0.791 | deleterious | N | 0.476141725 | None | None | I |
| R/I | 0.3084 | likely_benign | 0.2433 | benign | 0.09 | Stabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| R/K | 0.1232 | likely_benign | 0.1082 | benign | -0.672 | Destabilizing | 0.998 | D | 0.615 | neutral | None | None | None | None | I |
| R/L | 0.3094 | likely_benign | 0.2371 | benign | 0.09 | Stabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.447002706 | None | None | I |
| R/M | 0.3775 | ambiguous | 0.2911 | benign | -0.408 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| R/N | 0.7787 | likely_pathogenic | 0.6911 | pathogenic | -0.346 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| R/P | 0.635 | likely_pathogenic | 0.5311 | ambiguous | -0.17 | Destabilizing | 1.0 | D | 0.741 | deleterious | N | 0.482424788 | None | None | I |
| R/Q | 0.1418 | likely_benign | 0.117 | benign | -0.416 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| R/S | 0.7244 | likely_pathogenic | 0.6018 | pathogenic | -1.059 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | N | 0.483712867 | None | None | I |
| R/T | 0.388 | ambiguous | 0.2734 | benign | -0.725 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| R/V | 0.3966 | ambiguous | 0.3066 | benign | -0.17 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/W | 0.2962 | likely_benign | 0.2247 | benign | -0.21 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| R/Y | 0.5102 | ambiguous | 0.4308 | ambiguous | 0.067 | Stabilizing | 1.0 | D | 0.763 | deleterious | 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.