Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4629 | 14110;14111;14112 | chr2:178739348;178739347;178739346 | chr2:179604075;179604074;179604073 |
| N2AB | 4312 | 13159;13160;13161 | chr2:178739348;178739347;178739346 | chr2:179604075;179604074;179604073 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 4266 | 13021;13022;13023 | chr2:178739348;178739347;178739346 | chr2:179604075;179604074;179604073 |
| Novex-1 | 4391 | 13396;13397;13398 | chr2:178739348;178739347;178739346 | chr2:179604075;179604074;179604073 |
| Novex-2 | 4458 | 13597;13598;13599 | chr2:178739348;178739347;178739346 | chr2:179604075;179604074;179604073 |
| 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/T | rs994541516  |
-2.773 | 1.0 | D | 0.779 | 0.6 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs994541516 |
-2.773 | 1.0 | D | 0.779 | 0.6 | None | gnomAD-4.0.0 | 1.36842E-06 | None | None | None | None | N | None | 2.98704E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99446E-07 | 0 | 0 |
| I/V | rs774964232 |
-1.677 | 0.993 | N | 0.339 | 0.219 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/V | rs774964232 |
-1.677 | 0.993 | N | 0.339 | 0.219 | None | gnomAD-4.0.0 | 1.59126E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85804E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.7191 | likely_pathogenic | 0.7683 | pathogenic | -2.618 | Highly Destabilizing | 0.999 | D | 0.667 | neutral | None | None | None | None | N |
| I/C | 0.8733 | likely_pathogenic | 0.8894 | pathogenic | -2.372 | Highly Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | N |
| I/D | 0.9829 | likely_pathogenic | 0.9881 | pathogenic | -3.464 | Highly Destabilizing | 1.0 | D | 0.856 | deleterious | None | None | None | None | N |
| I/E | 0.9611 | likely_pathogenic | 0.9724 | pathogenic | -3.277 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| I/F | 0.332 | likely_benign | 0.3676 | ambiguous | -1.514 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| I/G | 0.9483 | likely_pathogenic | 0.9602 | pathogenic | -3.1 | Highly Destabilizing | 1.0 | D | 0.852 | deleterious | None | None | None | None | N |
| I/H | 0.9437 | likely_pathogenic | 0.9576 | pathogenic | -2.457 | Highly Destabilizing | 1.0 | D | 0.875 | deleterious | None | None | None | None | N |
| I/K | 0.9246 | likely_pathogenic | 0.9414 | pathogenic | -2.006 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | D | 0.707780245 | None | None | N |
| I/L | 0.1912 | likely_benign | 0.2176 | benign | -1.223 | Destabilizing | 0.993 | D | 0.407 | neutral | N | 0.51131086 | None | None | N |
| I/M | 0.1647 | likely_benign | 0.1797 | benign | -1.421 | Destabilizing | 1.0 | D | 0.791 | deleterious | D | 0.645341711 | None | None | N |
| I/N | 0.8642 | likely_pathogenic | 0.9001 | pathogenic | -2.406 | Highly Destabilizing | 1.0 | D | 0.874 | deleterious | None | None | None | None | N |
| I/P | 0.9802 | likely_pathogenic | 0.985 | pathogenic | -1.671 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| I/Q | 0.9329 | likely_pathogenic | 0.9488 | pathogenic | -2.331 | Highly Destabilizing | 1.0 | D | 0.883 | deleterious | None | None | None | None | N |
| I/R | 0.8901 | likely_pathogenic | 0.9138 | pathogenic | -1.643 | Destabilizing | 1.0 | D | 0.871 | deleterious | D | 0.707780245 | None | None | N |
| I/S | 0.8082 | likely_pathogenic | 0.8507 | pathogenic | -3.001 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/T | 0.7328 | likely_pathogenic | 0.7842 | pathogenic | -2.684 | Highly Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.561423108 | None | None | N |
| I/V | 0.0881 | likely_benign | 0.0932 | benign | -1.671 | Destabilizing | 0.993 | D | 0.339 | neutral | N | 0.48199215 | None | None | N |
| I/W | 0.957 | likely_pathogenic | 0.9665 | pathogenic | -1.904 | Destabilizing | 1.0 | D | 0.855 | deleterious | None | None | None | None | N |
| I/Y | 0.8367 | likely_pathogenic | 0.8641 | pathogenic | -1.702 | Destabilizing | 1.0 | D | 0.837 | deleterious | 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.