Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6494 | 19705;19706;19707 | chr2:178728344;178728343;178728342 | chr2:179593071;179593070;179593069 |
| N2AB | 6177 | 18754;18755;18756 | chr2:178728344;178728343;178728342 | chr2:179593071;179593070;179593069 |
| N2A | 5250 | 15973;15974;15975 | chr2:178728344;178728343;178728342 | chr2:179593071;179593070;179593069 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/R | rs376857772  |
-0.261 | 0.983 | N | 0.632 | 0.33 | None | gnomAD-2.1.1 | 9.52E-05 | None | None | None | None | N | None | 1.67434E-04 | 0 | None | 0 | 1.14919E-03 | None | 0 | None | 0 | 0 | 0 |
| L/R | rs376857772 |
-0.261 | 0.983 | N | 0.632 | 0.33 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 1.1592E-03 | None | 0 | 0 | 0 | 0 | 0 |
| L/R | rs376857772 |
-0.261 | 0.983 | N | 0.632 | 0.33 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| L/R | rs376857772 |
-0.261 | 0.983 | N | 0.632 | 0.33 | None | gnomAD-4.0.0 | 2.67282E-05 | None | None | None | None | N | None | 8.01946E-05 | 0 | None | 0 | 6.03865E-04 | None | 0 | 0 | 8.48764E-07 | 0 | 1.44662E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1995 | likely_benign | 0.2076 | benign | -1.028 | Destabilizing | 0.845 | D | 0.445 | neutral | None | None | None | None | N |
| L/C | 0.6044 | likely_pathogenic | 0.6226 | pathogenic | -0.875 | Destabilizing | 0.999 | D | 0.514 | neutral | None | None | None | None | N |
| L/D | 0.8104 | likely_pathogenic | 0.8102 | pathogenic | -0.139 | Destabilizing | 0.996 | D | 0.718 | prob.delet. | None | None | None | None | N |
| L/E | 0.3821 | ambiguous | 0.3884 | ambiguous | -0.174 | Destabilizing | 0.987 | D | 0.709 | prob.delet. | None | None | None | None | N |
| L/F | 0.2006 | likely_benign | 0.2087 | benign | -0.69 | Destabilizing | 0.975 | D | 0.441 | neutral | None | None | None | None | N |
| L/G | 0.6089 | likely_pathogenic | 0.6417 | pathogenic | -1.28 | Destabilizing | 0.987 | D | 0.706 | prob.neutral | None | None | None | None | N |
| L/H | 0.311 | likely_benign | 0.3203 | benign | -0.404 | Destabilizing | 0.999 | D | 0.739 | prob.delet. | None | None | None | None | N |
| L/I | 0.0861 | likely_benign | 0.0877 | benign | -0.452 | Destabilizing | 0.128 | N | 0.325 | neutral | None | None | None | None | N |
| L/K | 0.2678 | likely_benign | 0.2784 | benign | -0.623 | Destabilizing | 0.987 | D | 0.625 | neutral | None | None | None | None | N |
| L/M | 0.1487 | likely_benign | 0.1473 | benign | -0.494 | Destabilizing | 0.983 | D | 0.468 | neutral | N | 0.463694285 | None | None | N |
| L/N | 0.5552 | ambiguous | 0.5698 | pathogenic | -0.487 | Destabilizing | 0.996 | D | 0.71 | prob.delet. | None | None | None | None | N |
| L/P | 0.3656 | ambiguous | 0.3698 | ambiguous | -0.61 | Destabilizing | 0.994 | D | 0.716 | prob.delet. | N | 0.51069632 | None | None | N |
| L/Q | 0.1658 | likely_benign | 0.1746 | benign | -0.647 | Destabilizing | 0.994 | D | 0.627 | neutral | N | 0.507368013 | None | None | N |
| L/R | 0.1803 | likely_benign | 0.1924 | benign | -0.076 | Destabilizing | 0.983 | D | 0.632 | neutral | N | 0.513024549 | None | None | N |
| L/S | 0.299 | likely_benign | 0.3107 | benign | -1.098 | Destabilizing | 0.987 | D | 0.617 | neutral | None | None | None | None | N |
| L/T | 0.2136 | likely_benign | 0.2147 | benign | -1.011 | Destabilizing | 0.975 | D | 0.49 | neutral | None | None | None | None | N |
| L/V | 0.0875 | likely_benign | 0.0912 | benign | -0.61 | Destabilizing | 0.025 | N | 0.223 | neutral | N | 0.437062566 | None | None | N |
| L/W | 0.3046 | likely_benign | 0.3053 | benign | -0.698 | Destabilizing | 0.999 | D | 0.706 | prob.neutral | None | None | None | None | N |
| L/Y | 0.4776 | ambiguous | 0.492 | ambiguous | -0.472 | Destabilizing | 0.987 | D | 0.489 | neutral | 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.