Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27640 | 83143;83144;83145 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| N2AB | 25999 | 78220;78221;78222 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| N2A | 25072 | 75439;75440;75441 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| N2B | 18575 | 55948;55949;55950 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| Novex-1 | 18700 | 56323;56324;56325 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| Novex-2 | 18767 | 56524;56525;56526 | chr2:178563214;178563213;178563212 | chr2:179427941;179427940;179427939 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1553571185  |
None | 0.175 | N | 0.51 | 0.109 | 0.270889551736 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1553571185 |
None | 0.175 | N | 0.51 | 0.109 | 0.270889551736 | gnomAD-4.0.0 | 2.03002E-06 | None | None | None | None | N | None | 0 | 6.15915E-05 | None | 0 | 0 | None | 0 | 0 | 1.20494E-06 | 0 | 0 |
| T/N | None | None | 0.001 | N | 0.18 | 0.104 | 0.218112801441 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/S | rs1553571185 |
None | None | N | 0.096 | 0.088 | 0.112648838833 | gnomAD-4.0.0 | 1.59141E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85881E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0648 | likely_benign | 0.0672 | benign | -1.003 | Destabilizing | 0.001 | N | 0.068 | neutral | N | 0.467231623 | None | None | N |
| T/C | 0.1893 | likely_benign | 0.2188 | benign | -0.625 | Destabilizing | 0.883 | D | 0.462 | neutral | None | None | None | None | N |
| T/D | 0.3147 | likely_benign | 0.2934 | benign | -0.782 | Destabilizing | 0.124 | N | 0.423 | neutral | None | None | None | None | N |
| T/E | 0.2082 | likely_benign | 0.194 | benign | -0.681 | Destabilizing | 0.055 | N | 0.405 | neutral | None | None | None | None | N |
| T/F | 0.2058 | likely_benign | 0.2111 | benign | -0.731 | Destabilizing | 0.667 | D | 0.48 | neutral | None | None | None | None | N |
| T/G | 0.1739 | likely_benign | 0.175 | benign | -1.364 | Destabilizing | 0.055 | N | 0.352 | neutral | None | None | None | None | N |
| T/H | 0.1579 | likely_benign | 0.1516 | benign | -1.553 | Destabilizing | 0.002 | N | 0.272 | neutral | None | None | None | None | N |
| T/I | 0.1156 | likely_benign | 0.1152 | benign | -0.093 | Destabilizing | 0.175 | N | 0.51 | neutral | N | 0.477064594 | None | None | N |
| T/K | 0.1394 | likely_benign | 0.1276 | benign | -0.836 | Destabilizing | 0.055 | N | 0.407 | neutral | None | None | None | None | N |
| T/L | 0.0915 | likely_benign | 0.0924 | benign | -0.093 | Destabilizing | 0.104 | N | 0.409 | neutral | None | None | None | None | N |
| T/M | 0.0834 | likely_benign | 0.0831 | benign | 0.047 | Stabilizing | 0.667 | D | 0.475 | neutral | None | None | None | None | N |
| T/N | 0.1068 | likely_benign | 0.1085 | benign | -1.097 | Destabilizing | 0.001 | N | 0.18 | neutral | N | 0.501845629 | None | None | N |
| T/P | 0.6217 | likely_pathogenic | 0.549 | ambiguous | -0.363 | Destabilizing | 0.301 | N | 0.51 | neutral | D | 0.524148883 | None | None | N |
| T/Q | 0.1376 | likely_benign | 0.1288 | benign | -1.05 | Destabilizing | 0.004 | N | 0.221 | neutral | None | None | None | None | N |
| T/R | 0.1117 | likely_benign | 0.0991 | benign | -0.791 | Destabilizing | 0.124 | N | 0.454 | neutral | None | None | None | None | N |
| T/S | 0.0894 | likely_benign | 0.094 | benign | -1.349 | Destabilizing | None | N | 0.096 | neutral | N | 0.501266839 | None | None | N |
| T/V | 0.0887 | likely_benign | 0.0941 | benign | -0.363 | Destabilizing | 0.22 | N | 0.349 | neutral | None | None | None | None | N |
| T/W | 0.4907 | ambiguous | 0.4617 | ambiguous | -0.773 | Destabilizing | 0.958 | D | 0.476 | neutral | None | None | None | None | N |
| T/Y | 0.2153 | likely_benign | 0.2094 | benign | -0.494 | Destabilizing | 0.331 | N | 0.5 | neutral | 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.