Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32278 | 97057;97058;97059 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| N2AB | 30637 | 92134;92135;92136 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| N2A | 29710 | 89353;89354;89355 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| N2B | 23213 | 69862;69863;69864 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| Novex-1 | 23338 | 70237;70238;70239 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| Novex-2 | 23405 | 70438;70439;70440 | chr2:178543141;178543140;178543139 | chr2:179407868;179407867;179407866 |
| 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/G | None | None | 1.0 | N | 0.802 | 0.563 | 0.609541433255 | gnomAD-4.0.0 | 1.36931E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.80024E-06 | 0 | 0 |
| R/S | rs558927011  |
-1.751 | 1.0 | N | 0.775 | 0.419 | 0.321108458156 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.56E-05 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs558927011 |
-1.751 | 1.0 | N | 0.775 | 0.419 | 0.321108458156 | gnomAD-4.0.0 | 6.84784E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.65788E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4957 | ambiguous | 0.446 | ambiguous | -1.513 | Destabilizing | 0.999 | D | 0.705 | prob.neutral | None | None | None | None | I |
| R/C | 0.1752 | likely_benign | 0.1415 | benign | -1.653 | Destabilizing | 1.0 | D | 0.806 | deleterious | None | None | None | None | I |
| R/D | 0.9307 | likely_pathogenic | 0.9198 | pathogenic | -0.94 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| R/E | 0.6703 | likely_pathogenic | 0.6215 | pathogenic | -0.751 | Destabilizing | 0.999 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/F | 0.6277 | likely_pathogenic | 0.5753 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.829 | deleterious | None | None | None | None | I |
| R/G | 0.4204 | ambiguous | 0.3815 | ambiguous | -1.84 | Destabilizing | 1.0 | D | 0.802 | deleterious | N | 0.511010789 | None | None | I |
| R/H | 0.1689 | likely_benign | 0.1526 | benign | -1.894 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| R/I | 0.3933 | ambiguous | 0.3304 | benign | -0.588 | Destabilizing | 1.0 | D | 0.83 | deleterious | None | None | None | None | I |
| R/K | 0.1455 | likely_benign | 0.1235 | benign | -1.438 | Destabilizing | 0.997 | D | 0.693 | prob.neutral | N | 0.501471909 | None | None | I |
| R/L | 0.337 | likely_benign | 0.2967 | benign | -0.588 | Destabilizing | 1.0 | D | 0.802 | deleterious | None | None | None | None | I |
| R/M | 0.3317 | likely_benign | 0.2882 | benign | -1.086 | Destabilizing | 1.0 | D | 0.795 | deleterious | N | 0.509651462 | None | None | I |
| R/N | 0.8328 | likely_pathogenic | 0.8021 | pathogenic | -1.312 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| R/P | 0.9766 | likely_pathogenic | 0.9775 | pathogenic | -0.883 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | I |
| R/Q | 0.1389 | likely_benign | 0.1233 | benign | -1.138 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| R/S | 0.5597 | ambiguous | 0.5035 | ambiguous | -2.012 | Highly Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.505552364 | None | None | I |
| R/T | 0.3427 | ambiguous | 0.2858 | benign | -1.631 | Destabilizing | 1.0 | D | 0.777 | deleterious | N | 0.465937508 | None | None | I |
| R/V | 0.4677 | ambiguous | 0.4023 | ambiguous | -0.883 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| R/W | 0.225 | likely_benign | 0.2163 | benign | -0.556 | Destabilizing | 1.0 | D | 0.8 | deleterious | N | 0.504934403 | None | None | I |
| R/Y | 0.5132 | ambiguous | 0.4782 | ambiguous | -0.317 | Destabilizing | 1.0 | D | 0.832 | 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.