Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32577 | 97954;97955;97956 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| N2AB | 30936 | 93031;93032;93033 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| N2A | 30009 | 90250;90251;90252 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| N2B | 23512 | 70759;70760;70761 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| Novex-1 | 23637 | 71134;71135;71136 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| Novex-2 | 23704 | 71335;71336;71337 | chr2:178541348;178541347;178541346 | chr2:179406075;179406074;179406073 |
| 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 | rs1369862487  |
-1.347 | 0.916 | N | 0.809 | 0.509 | 0.770098793453 | gnomAD-2.1.1 | 4.72E-06 | None | None | None | None | I | None | 0 | 3.32E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/N | rs1369862487 |
-1.347 | 0.916 | N | 0.809 | 0.509 | 0.770098793453 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs1369862487 |
-1.347 | 0.916 | N | 0.809 | 0.509 | 0.770098793453 | gnomAD-4.0.0 | 2.65293E-06 | None | None | None | None | I | None | 0 | 3.61063E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | rs1369862487 |
-2.126 | 0.638 | N | 0.688 | 0.451 | 0.696367886986 | gnomAD-2.1.1 | 4.72E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.09E-05 | 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 | 0.5822 | likely_pathogenic | 0.6157 | pathogenic | -1.659 | Destabilizing | 0.25 | N | 0.539 | neutral | None | None | None | None | I |
| I/C | 0.726 | likely_pathogenic | 0.721 | pathogenic | -1.338 | Destabilizing | 0.947 | D | 0.715 | prob.delet. | None | None | None | None | I |
| I/D | 0.9222 | likely_pathogenic | 0.9421 | pathogenic | -0.865 | Destabilizing | 0.826 | D | 0.799 | deleterious | None | None | None | None | I |
| I/E | 0.6941 | likely_pathogenic | 0.716 | pathogenic | -0.838 | Destabilizing | 0.826 | D | 0.774 | deleterious | None | None | None | None | I |
| I/F | 0.2665 | likely_benign | 0.2879 | benign | -1.192 | Destabilizing | 0.638 | D | 0.623 | neutral | N | 0.484387658 | None | None | I |
| I/G | 0.8734 | likely_pathogenic | 0.9007 | pathogenic | -1.987 | Destabilizing | 0.826 | D | 0.763 | deleterious | None | None | None | None | I |
| I/H | 0.7833 | likely_pathogenic | 0.8081 | pathogenic | -1.159 | Destabilizing | 0.982 | D | 0.791 | deleterious | None | None | None | None | I |
| I/K | 0.6392 | likely_pathogenic | 0.6777 | pathogenic | -0.947 | Destabilizing | 0.826 | D | 0.777 | deleterious | None | None | None | None | I |
| I/L | 0.1358 | likely_benign | 0.1473 | benign | -0.825 | Destabilizing | 0.043 | N | 0.381 | neutral | N | 0.412178056 | None | None | I |
| I/M | 0.1076 | likely_benign | 0.1136 | benign | -0.805 | Destabilizing | 0.638 | D | 0.606 | neutral | N | 0.469823637 | None | None | I |
| I/N | 0.6238 | likely_pathogenic | 0.7038 | pathogenic | -0.826 | Destabilizing | 0.916 | D | 0.809 | deleterious | N | 0.485081091 | None | None | I |
| I/P | 0.9898 | likely_pathogenic | 0.9916 | pathogenic | -1.073 | Destabilizing | 0.935 | D | 0.805 | deleterious | None | None | None | None | I |
| I/Q | 0.5901 | likely_pathogenic | 0.6122 | pathogenic | -0.993 | Destabilizing | 0.935 | D | 0.803 | deleterious | None | None | None | None | I |
| I/R | 0.5612 | ambiguous | 0.6157 | pathogenic | -0.463 | Destabilizing | 0.826 | D | 0.808 | deleterious | None | None | None | None | I |
| I/S | 0.5869 | likely_pathogenic | 0.6407 | pathogenic | -1.571 | Destabilizing | 0.638 | D | 0.688 | prob.neutral | N | 0.473517303 | None | None | I |
| I/T | 0.3945 | ambiguous | 0.4124 | ambiguous | -1.422 | Destabilizing | 0.201 | N | 0.629 | neutral | N | 0.459606643 | None | None | I |
| I/V | 0.0772 | likely_benign | 0.0761 | benign | -1.073 | Destabilizing | 0.001 | N | 0.223 | neutral | N | 0.345198129 | None | None | I |
| I/W | 0.847 | likely_pathogenic | 0.8574 | pathogenic | -1.208 | Destabilizing | 0.982 | D | 0.725 | prob.delet. | None | None | None | None | I |
| I/Y | 0.6949 | likely_pathogenic | 0.7218 | pathogenic | -0.957 | Destabilizing | 0.826 | D | 0.747 | 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.