Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31355 | 94288;94289;94290 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| N2AB | 29714 | 89365;89366;89367 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| N2A | 28787 | 86584;86585;86586 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| N2B | 22290 | 67093;67094;67095 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| Novex-1 | 22415 | 67468;67469;67470 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| Novex-2 | 22482 | 67669;67670;67671 | chr2:178547563;178547562;178547561 | chr2:179412290;179412289;179412288 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.027 | N | 0.346 | 0.143 | 0.355242300401 | gnomAD-4.0.0 | 6.84203E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99447E-07 | 0 | 0 |
| A/P | None | None | 0.317 | N | 0.327 | 0.161 | 0.482137172311 | gnomAD-4.0.0 | 6.84202E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99449E-07 | 0 | 0 |
| A/T | rs780964196  |
-0.336 | 0.002 | N | 0.223 | 0.061 | 0.30921473904 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.1162E-04 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs780964196 |
-0.336 | 0.002 | N | 0.223 | 0.061 | 0.30921473904 | gnomAD-4.0.0 | 1.3684E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.04159E-05 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs370666551 |
-0.121 | 0.117 | N | 0.291 | 0.108 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.69E-05 | 1.40371E-04 |
| A/V | rs370666551 |
-0.121 | 0.117 | N | 0.291 | 0.108 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/V | rs370666551 |
-0.121 | 0.117 | N | 0.291 | 0.108 | None | gnomAD-4.0.0 | 3.03654E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.9837E-05 | 0 | 3.20236E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4076 | ambiguous | 0.3618 | ambiguous | -0.773 | Destabilizing | 0.824 | D | 0.327 | neutral | None | None | None | None | I |
| A/D | 0.4034 | ambiguous | 0.3782 | ambiguous | -0.553 | Destabilizing | 0.062 | N | 0.303 | neutral | N | 0.435438918 | None | None | I |
| A/E | 0.3606 | ambiguous | 0.3433 | ambiguous | -0.679 | Destabilizing | 0.081 | N | 0.292 | neutral | None | None | None | None | I |
| A/F | 0.3833 | ambiguous | 0.3731 | ambiguous | -1.043 | Destabilizing | 0.555 | D | 0.408 | neutral | None | None | None | None | I |
| A/G | 0.1596 | likely_benign | 0.1373 | benign | -0.73 | Destabilizing | 0.027 | N | 0.346 | neutral | N | 0.407772314 | None | None | I |
| A/H | 0.5023 | ambiguous | 0.4569 | ambiguous | -0.71 | Destabilizing | 0.001 | N | 0.337 | neutral | None | None | None | None | I |
| A/I | 0.1925 | likely_benign | 0.2109 | benign | -0.51 | Destabilizing | 0.38 | N | 0.325 | neutral | None | None | None | None | I |
| A/K | 0.5681 | likely_pathogenic | 0.5406 | ambiguous | -0.846 | Destabilizing | 0.081 | N | 0.265 | neutral | None | None | None | None | I |
| A/L | 0.1617 | likely_benign | 0.1532 | benign | -0.51 | Destabilizing | 0.149 | N | 0.297 | neutral | None | None | None | None | I |
| A/M | 0.1849 | likely_benign | 0.1851 | benign | -0.5 | Destabilizing | 0.935 | D | 0.307 | neutral | None | None | None | None | I |
| A/N | 0.2118 | likely_benign | 0.1948 | benign | -0.484 | Destabilizing | 0.001 | N | 0.273 | neutral | None | None | None | None | I |
| A/P | 0.6999 | likely_pathogenic | 0.6054 | pathogenic | -0.51 | Destabilizing | 0.317 | N | 0.327 | neutral | N | 0.494180577 | None | None | I |
| A/Q | 0.3604 | ambiguous | 0.3239 | benign | -0.752 | Destabilizing | 0.38 | N | 0.319 | neutral | None | None | None | None | I |
| A/R | 0.5443 | ambiguous | 0.5138 | ambiguous | -0.366 | Destabilizing | 0.38 | N | 0.324 | neutral | None | None | None | None | I |
| A/S | 0.0838 | likely_benign | 0.0788 | benign | -0.743 | Destabilizing | None | N | 0.131 | neutral | N | 0.395861809 | None | None | I |
| A/T | 0.0678 | likely_benign | 0.0711 | benign | -0.786 | Destabilizing | 0.002 | N | 0.223 | neutral | N | 0.394536445 | None | None | I |
| A/V | 0.1069 | likely_benign | 0.1115 | benign | -0.51 | Destabilizing | 0.117 | N | 0.291 | neutral | N | 0.439943447 | None | None | I |
| A/W | 0.793 | likely_pathogenic | 0.7648 | pathogenic | -1.193 | Destabilizing | 0.935 | D | 0.529 | neutral | None | None | None | None | I |
| A/Y | 0.5172 | ambiguous | 0.4785 | ambiguous | -0.854 | Destabilizing | 0.38 | N | 0.419 | neutral | 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.