Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33645 | 101158;101159;101160 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| N2AB | 32004 | 96235;96236;96237 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| N2A | 31077 | 93454;93455;93456 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| N2B | 24580 | 73963;73964;73965 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| Novex-1 | 24705 | 74338;74339;74340 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| Novex-2 | 24772 | 74539;74540;74541 | chr2:178535682;178535681;178535680 | chr2:179400409;179400408;179400407 |
| 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/F | rs770564631  |
-0.978 | 1.0 | N | 0.639 | 0.461 | 0.628336401329 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| I/F | rs770564631 |
-0.978 | 1.0 | N | 0.639 | 0.461 | 0.628336401329 | 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 |
| I/F | rs770564631 |
-0.978 | 1.0 | N | 0.639 | 0.461 | 0.628336401329 | gnomAD-4.0.0 | 3.84328E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17892E-06 | 0 | 0 |
| I/M | None | None | 0.999 | D | 0.616 | 0.222 | 0.585443171169 | gnomAD-4.0.0 | 6.1578E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.0952E-06 | 0 | 0 |
| I/T | rs1691122831 |
None | 1.0 | N | 0.631 | 0.452 | 0.672566338644 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1691122831 |
None | 1.0 | N | 0.631 | 0.452 | 0.672566338644 | gnomAD-4.0.0 | 2.4788E-06 | None | None | None | None | I | None | 1.33529E-05 | 0 | None | 0 | 2.22777E-05 | None | 0 | 0 | 8.4761E-07 | 0 | 1.60118E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.9409 | likely_pathogenic | 0.8864 | pathogenic | -1.278 | Destabilizing | 1.0 | D | 0.473 | neutral | None | None | None | None | I |
| I/C | 0.9888 | likely_pathogenic | 0.9817 | pathogenic | -0.771 | Destabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| I/D | 0.9952 | likely_pathogenic | 0.99 | pathogenic | -0.614 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | None | I |
| I/E | 0.9865 | likely_pathogenic | 0.9698 | pathogenic | -0.654 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | I |
| I/F | 0.7352 | likely_pathogenic | 0.6331 | pathogenic | -0.952 | Destabilizing | 1.0 | D | 0.639 | neutral | N | 0.48717404 | None | None | I |
| I/G | 0.9926 | likely_pathogenic | 0.9864 | pathogenic | -1.547 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| I/H | 0.9776 | likely_pathogenic | 0.9625 | pathogenic | -0.728 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | I |
| I/K | 0.9749 | likely_pathogenic | 0.9521 | pathogenic | -0.802 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | I |
| I/L | 0.5259 | ambiguous | 0.4013 | ambiguous | -0.648 | Destabilizing | 0.949 | D | 0.266 | neutral | N | 0.446957925 | None | None | I |
| I/M | 0.4321 | ambiguous | 0.3218 | benign | -0.476 | Destabilizing | 0.999 | D | 0.616 | neutral | D | 0.525842783 | None | None | I |
| I/N | 0.9521 | likely_pathogenic | 0.9182 | pathogenic | -0.581 | Destabilizing | 1.0 | D | 0.755 | deleterious | N | 0.484572164 | None | None | I |
| I/P | 0.9968 | likely_pathogenic | 0.9955 | pathogenic | -0.824 | Destabilizing | 1.0 | D | 0.759 | deleterious | None | None | None | None | I |
| I/Q | 0.9719 | likely_pathogenic | 0.9476 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| I/R | 0.9584 | likely_pathogenic | 0.9224 | pathogenic | -0.184 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| I/S | 0.9481 | likely_pathogenic | 0.9077 | pathogenic | -1.16 | Destabilizing | 1.0 | D | 0.724 | prob.delet. | N | 0.450592876 | None | None | I |
| I/T | 0.8692 | likely_pathogenic | 0.7778 | pathogenic | -1.088 | Destabilizing | 1.0 | D | 0.631 | neutral | N | 0.466869051 | None | None | I |
| I/V | 0.3525 | ambiguous | 0.2755 | benign | -0.824 | Destabilizing | 0.961 | D | 0.277 | neutral | N | 0.467159839 | None | None | I |
| I/W | 0.9832 | likely_pathogenic | 0.978 | pathogenic | -0.978 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | I |
| I/Y | 0.9611 | likely_pathogenic | 0.942 | pathogenic | -0.754 | Destabilizing | 0.999 | D | 0.715 | prob.delet. | 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.