Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24729 | 74410;74411;74412 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| N2AB | 23088 | 69487;69488;69489 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| N2A | 22161 | 66706;66707;66708 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| N2B | 15664 | 47215;47216;47217 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| Novex-1 | 15789 | 47590;47591;47592 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| Novex-2 | 15856 | 47791;47792;47793 | chr2:178571947;178571946;178571945 | chr2:179436674;179436673;179436672 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs372007344  |
-0.502 | 1.0 | N | 0.624 | 0.354 | None | gnomAD-2.1.1 | 2.51E-05 | None | None | None | None | I | None | 4.14E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 0 |
| A/T | rs372007344 |
-0.502 | 1.0 | N | 0.624 | 0.354 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| A/T | rs372007344 |
-0.502 | 1.0 | N | 0.624 | 0.354 | None | gnomAD-4.0.0 | 1.36376E-05 | None | None | None | None | I | None | 1.33547E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.78028E-05 | 0 | 0 |
| A/V | rs1162562703 |
-0.291 | 1.0 | N | 0.541 | 0.39 | 0.305086939656 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| A/V | rs1162562703 |
-0.291 | 1.0 | N | 0.541 | 0.39 | 0.305086939656 | gnomAD-4.0.0 | 3.18464E-06 | None | None | None | None | I | None | 0 | 0 | None | 4.77008E-05 | 0 | None | 0 | 0 | 0 | 1.43295E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5895 | likely_pathogenic | 0.6273 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/D | 0.79 | likely_pathogenic | 0.8498 | pathogenic | -0.706 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| A/E | 0.5579 | ambiguous | 0.6403 | pathogenic | -0.836 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.466459966 | None | None | I |
| A/F | 0.6978 | likely_pathogenic | 0.7621 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| A/G | 0.3006 | likely_benign | 0.34 | benign | -0.69 | Destabilizing | 1.0 | D | 0.408 | neutral | N | 0.503145252 | None | None | I |
| A/H | 0.7475 | likely_pathogenic | 0.7986 | pathogenic | -0.732 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | I |
| A/I | 0.4927 | ambiguous | 0.5808 | pathogenic | -0.44 | Destabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | I |
| A/K | 0.7259 | likely_pathogenic | 0.7935 | pathogenic | -0.913 | Destabilizing | 1.0 | D | 0.656 | neutral | None | None | None | None | I |
| A/L | 0.4282 | ambiguous | 0.4872 | ambiguous | -0.44 | Destabilizing | 1.0 | D | 0.599 | neutral | None | None | None | None | I |
| A/M | 0.4649 | ambiguous | 0.5375 | ambiguous | -0.377 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| A/N | 0.6281 | likely_pathogenic | 0.682 | pathogenic | -0.531 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| A/P | 0.7819 | likely_pathogenic | 0.8412 | pathogenic | -0.446 | Destabilizing | 1.0 | D | 0.669 | neutral | N | 0.513544624 | None | None | I |
| A/Q | 0.532 | ambiguous | 0.5921 | pathogenic | -0.816 | Destabilizing | 1.0 | D | 0.67 | neutral | None | None | None | None | I |
| A/R | 0.6328 | likely_pathogenic | 0.7014 | pathogenic | -0.416 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | I |
| A/S | 0.1292 | likely_benign | 0.145 | benign | -0.779 | Destabilizing | 1.0 | D | 0.467 | neutral | N | 0.490283762 | None | None | I |
| A/T | 0.2295 | likely_benign | 0.2912 | benign | -0.829 | Destabilizing | 1.0 | D | 0.624 | neutral | N | 0.464023453 | None | None | I |
| A/V | 0.2143 | likely_benign | 0.2728 | benign | -0.446 | Destabilizing | 1.0 | D | 0.541 | neutral | N | 0.462979731 | None | None | I |
| A/W | 0.9394 | likely_pathogenic | 0.9573 | pathogenic | -1.177 | Destabilizing | 1.0 | D | 0.785 | deleterious | None | None | None | None | I |
| A/Y | 0.7939 | likely_pathogenic | 0.8376 | pathogenic | -0.833 | Destabilizing | 1.0 | D | 0.733 | 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.