Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26998 | 81217;81218;81219 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| N2AB | 25357 | 76294;76295;76296 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| N2A | 24430 | 73513;73514;73515 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| N2B | 17933 | 54022;54023;54024 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| Novex-1 | 18058 | 54397;54398;54399 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| Novex-2 | 18125 | 54598;54599;54600 | chr2:178565140;178565139;178565138 | chr2:179429867;179429866;179429865 |
| 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/T | rs373572123  |
-0.306 | 0.012 | N | 0.221 | 0.044 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 0 |
| A/T | rs373572123 |
-0.306 | 0.012 | N | 0.221 | 0.044 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| A/T | rs373572123 |
-0.306 | 0.012 | N | 0.221 | 0.044 | None | gnomAD-4.0.0 | 4.9589E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.08663E-06 | 1.0988E-05 | 1.60164E-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 | 0.345 | ambiguous | 0.3452 | ambiguous | -0.785 | Destabilizing | 0.676 | D | 0.275 | neutral | None | None | None | None | I |
| A/D | 0.1465 | likely_benign | 0.1501 | benign | -0.59 | Destabilizing | None | N | 0.246 | neutral | N | 0.470034281 | None | None | I |
| A/E | 0.1105 | likely_benign | 0.1187 | benign | -0.729 | Destabilizing | None | N | 0.119 | neutral | None | None | None | None | I |
| A/F | 0.2242 | likely_benign | 0.2148 | benign | -0.849 | Destabilizing | 0.214 | N | 0.353 | neutral | None | None | None | None | I |
| A/G | 0.1176 | likely_benign | 0.1106 | benign | -0.384 | Destabilizing | 0.012 | N | 0.232 | neutral | N | 0.504109569 | None | None | I |
| A/H | 0.2783 | likely_benign | 0.2744 | benign | -0.375 | Destabilizing | 0.356 | N | 0.324 | neutral | None | None | None | None | I |
| A/I | 0.1152 | likely_benign | 0.1139 | benign | -0.345 | Destabilizing | None | N | 0.188 | neutral | None | None | None | None | I |
| A/K | 0.1839 | likely_benign | 0.1899 | benign | -0.776 | Destabilizing | None | N | 0.202 | neutral | None | None | None | None | I |
| A/L | 0.0862 | likely_benign | 0.0846 | benign | -0.345 | Destabilizing | 0.006 | N | 0.319 | neutral | None | None | None | None | I |
| A/M | 0.1421 | likely_benign | 0.1386 | benign | -0.499 | Destabilizing | 0.214 | N | 0.281 | neutral | None | None | None | None | I |
| A/N | 0.135 | likely_benign | 0.1272 | benign | -0.448 | Destabilizing | 0.038 | N | 0.408 | neutral | None | None | None | None | I |
| A/P | 0.1525 | likely_benign | 0.1416 | benign | -0.304 | Destabilizing | 0.106 | N | 0.372 | neutral | N | 0.475517458 | None | None | I |
| A/Q | 0.1579 | likely_benign | 0.1612 | benign | -0.707 | Destabilizing | 0.038 | N | 0.381 | neutral | None | None | None | None | I |
| A/R | 0.1986 | likely_benign | 0.2101 | benign | -0.294 | Destabilizing | 0.038 | N | 0.351 | neutral | None | None | None | None | I |
| A/S | 0.0807 | likely_benign | 0.079 | benign | -0.631 | Destabilizing | None | N | 0.059 | neutral | N | 0.44938965 | None | None | I |
| A/T | 0.0712 | likely_benign | 0.0697 | benign | -0.693 | Destabilizing | 0.012 | N | 0.221 | neutral | N | 0.482078071 | None | None | I |
| A/V | 0.0754 | likely_benign | 0.0748 | benign | -0.304 | Destabilizing | None | N | 0.065 | neutral | N | 0.441444957 | None | None | I |
| A/W | 0.5855 | likely_pathogenic | 0.569 | pathogenic | -1.005 | Destabilizing | 0.864 | D | 0.345 | neutral | None | None | None | None | I |
| A/Y | 0.3115 | likely_benign | 0.2995 | benign | -0.671 | Destabilizing | 0.356 | N | 0.351 | 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.