Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29344 | 88255;88256;88257 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| N2AB | 27703 | 83332;83333;83334 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| N2A | 26776 | 80551;80552;80553 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| N2B | 20279 | 61060;61061;61062 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| Novex-1 | 20404 | 61435;61436;61437 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| Novex-2 | 20471 | 61636;61637;61638 | chr2:178557124;178557123;178557122 | chr2:179421851;179421850;179421849 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/N | rs762659029  |
-1.86 | 0.484 | N | 0.697 | 0.422 | 0.825227375999 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 9.82E-05 | None | 0 | 0 | 0 |
| I/N | rs762659029 |
-1.86 | 0.484 | N | 0.697 | 0.422 | 0.825227375999 | gnomAD-4.0.0 | 7.52725E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.27569E-04 | 0 |
| I/T | rs762659029 |
-2.33 | 0.062 | N | 0.557 | 0.238 | 0.626322489162 | gnomAD-2.1.1 | 6.37E-05 | None | None | None | None | N | None | 2.2941E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs762659029 |
-2.33 | 0.062 | N | 0.557 | 0.238 | 0.626322489162 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs762659029 |
-2.33 | 0.062 | N | 0.557 | 0.238 | 0.626322489162 | gnomAD-4.0.0 | 1.85924E-06 | None | None | None | None | N | None | 4.00342E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.487 | ambiguous | 0.335 | benign | -1.93 | Destabilizing | None | N | 0.292 | neutral | None | None | None | None | N |
| I/C | 0.6925 | likely_pathogenic | 0.5736 | pathogenic | -1.591 | Destabilizing | 0.824 | D | 0.617 | neutral | None | None | None | None | N |
| I/D | 0.9398 | likely_pathogenic | 0.8818 | pathogenic | -1.022 | Destabilizing | 0.555 | D | 0.695 | prob.neutral | None | None | None | None | N |
| I/E | 0.8853 | likely_pathogenic | 0.8076 | pathogenic | -0.907 | Destabilizing | 0.38 | N | 0.703 | prob.neutral | None | None | None | None | N |
| I/F | 0.2938 | likely_benign | 0.2003 | benign | -1.116 | Destabilizing | 0.317 | N | 0.591 | neutral | N | 0.515227853 | None | None | N |
| I/G | 0.8474 | likely_pathogenic | 0.6942 | pathogenic | -2.362 | Highly Destabilizing | 0.081 | N | 0.668 | neutral | None | None | None | None | N |
| I/H | 0.8324 | likely_pathogenic | 0.7391 | pathogenic | -1.407 | Destabilizing | 0.935 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/K | 0.784 | likely_pathogenic | 0.6963 | pathogenic | -1.395 | Destabilizing | 0.38 | N | 0.701 | prob.neutral | None | None | None | None | N |
| I/L | 0.182 | likely_benign | 0.1404 | benign | -0.763 | Destabilizing | 0.012 | N | 0.497 | neutral | N | 0.464031028 | None | None | N |
| I/M | 0.165 | likely_benign | 0.1309 | benign | -0.837 | Destabilizing | 0.317 | N | 0.574 | neutral | D | 0.522137969 | None | None | N |
| I/N | 0.5937 | likely_pathogenic | 0.475 | ambiguous | -1.486 | Destabilizing | 0.484 | N | 0.697 | prob.neutral | N | 0.482969034 | None | None | N |
| I/P | 0.7084 | likely_pathogenic | 0.5266 | ambiguous | -1.123 | Destabilizing | 0.555 | D | 0.694 | prob.neutral | None | None | None | None | N |
| I/Q | 0.8088 | likely_pathogenic | 0.7068 | pathogenic | -1.461 | Destabilizing | 0.555 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/R | 0.7403 | likely_pathogenic | 0.6299 | pathogenic | -0.967 | Destabilizing | 0.555 | D | 0.696 | prob.neutral | None | None | None | None | N |
| I/S | 0.6038 | likely_pathogenic | 0.4495 | ambiguous | -2.282 | Highly Destabilizing | 0.062 | N | 0.597 | neutral | N | 0.475460616 | None | None | N |
| I/T | 0.4957 | ambiguous | 0.3791 | ambiguous | -2.014 | Highly Destabilizing | 0.062 | N | 0.557 | neutral | N | 0.520156457 | None | None | N |
| I/V | 0.069 | likely_benign | 0.0588 | benign | -1.123 | Destabilizing | None | N | 0.168 | neutral | N | 0.358111498 | None | None | N |
| I/W | 0.9098 | likely_pathogenic | 0.8359 | pathogenic | -1.197 | Destabilizing | 0.935 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6664 | likely_pathogenic | 0.5478 | ambiguous | -0.974 | Destabilizing | 0.555 | D | 0.627 | 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.