Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31863 | 95812;95813;95814 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| N2AB | 30222 | 90889;90890;90891 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| N2A | 29295 | 88108;88109;88110 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| N2B | 22798 | 68617;68618;68619 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| Novex-1 | 22923 | 68992;68993;68994 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| Novex-2 | 22990 | 69193;69194;69195 | chr2:178545523;178545522;178545521 | chr2:179410250;179410249;179410248 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.104 | N | 0.557 | 0.275 | 0.629112818682 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| V/L | None | None | 0.009 | N | 0.37 | 0.07 | 0.431931272081 | gnomAD-4.0.0 | 1.59153E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77269E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs1261237419  |
-0.684 | 0.497 | N | 0.626 | 0.177 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4157 | ambiguous | 0.4518 | ambiguous | -1.526 | Destabilizing | 0.104 | N | 0.557 | neutral | N | 0.520748316 | None | None | N |
| V/C | 0.7552 | likely_pathogenic | 0.7407 | pathogenic | -0.609 | Destabilizing | 0.968 | D | 0.721 | prob.delet. | None | None | None | None | N |
| V/D | 0.8696 | likely_pathogenic | 0.8759 | pathogenic | -2.271 | Highly Destabilizing | 0.726 | D | 0.809 | deleterious | None | None | None | None | N |
| V/E | 0.7948 | likely_pathogenic | 0.7915 | pathogenic | -2.02 | Highly Destabilizing | 0.667 | D | 0.767 | deleterious | N | 0.508001233 | None | None | N |
| V/F | 0.3658 | ambiguous | 0.3406 | ambiguous | -0.98 | Destabilizing | 0.567 | D | 0.73 | prob.delet. | None | None | None | None | N |
| V/G | 0.5537 | ambiguous | 0.5829 | pathogenic | -2.046 | Highly Destabilizing | 0.667 | D | 0.797 | deleterious | N | 0.468241686 | None | None | N |
| V/H | 0.8636 | likely_pathogenic | 0.8517 | pathogenic | -2.021 | Highly Destabilizing | 0.968 | D | 0.801 | deleterious | None | None | None | None | N |
| V/I | 0.0688 | likely_benign | 0.0686 | benign | -0.059 | Destabilizing | None | N | 0.208 | neutral | None | None | None | None | N |
| V/K | 0.808 | likely_pathogenic | 0.8129 | pathogenic | -1.064 | Destabilizing | 0.726 | D | 0.767 | deleterious | None | None | None | None | N |
| V/L | 0.2212 | likely_benign | 0.2046 | benign | -0.059 | Destabilizing | 0.009 | N | 0.37 | neutral | N | 0.499509039 | None | None | N |
| V/M | 0.2707 | likely_benign | 0.2574 | benign | 0.033 | Stabilizing | 0.497 | N | 0.626 | neutral | N | 0.502728676 | None | None | N |
| V/N | 0.6471 | likely_pathogenic | 0.6446 | pathogenic | -1.507 | Destabilizing | 0.89 | D | 0.817 | deleterious | None | None | None | None | N |
| V/P | 0.743 | likely_pathogenic | 0.7869 | pathogenic | -0.525 | Destabilizing | 0.89 | D | 0.744 | deleterious | None | None | None | None | N |
| V/Q | 0.7474 | likely_pathogenic | 0.7329 | pathogenic | -1.284 | Destabilizing | 0.89 | D | 0.765 | deleterious | None | None | None | None | N |
| V/R | 0.756 | likely_pathogenic | 0.7528 | pathogenic | -1.122 | Destabilizing | 0.726 | D | 0.817 | deleterious | None | None | None | None | N |
| V/S | 0.5628 | ambiguous | 0.5713 | pathogenic | -2.011 | Highly Destabilizing | 0.726 | D | 0.739 | prob.delet. | None | None | None | None | N |
| V/T | 0.4426 | ambiguous | 0.4536 | ambiguous | -1.622 | Destabilizing | 0.272 | N | 0.609 | neutral | None | None | None | None | N |
| V/W | 0.9324 | likely_pathogenic | 0.9217 | pathogenic | -1.606 | Destabilizing | 0.968 | D | 0.764 | deleterious | None | None | None | None | N |
| V/Y | 0.7997 | likely_pathogenic | 0.7736 | pathogenic | -1.092 | Destabilizing | 0.726 | D | 0.74 | 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.