Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9607 | 29044;29045;29046 | chr2:178707748;178707747;178707746 | chr2:179572475;179572474;179572473 |
| N2AB | 9290 | 28093;28094;28095 | chr2:178707748;178707747;178707746 | chr2:179572475;179572474;179572473 |
| N2A | 8363 | 25312;25313;25314 | chr2:178707748;178707747;178707746 | chr2:179572475;179572474;179572473 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | None | None | 0.001 | None | 0.149 | 0.064 | 0.119812018005 | gnomAD-4.0.0 | 6.84195E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99462E-07 | 0 | 0 |
| V/M | rs375807609  |
-0.471 | 0.095 | None | 0.237 | 0.027 | None | gnomAD-2.1.1 | 1.10543E-04 | None | None | None | None | N | None | 1.65371E-04 | 8.49E-05 | None | 0 | 1.07505E-03 | None | 3.27E-05 | None | 4E-05 | 7.79E-06 | 0 |
| V/M | rs375807609 |
-0.471 | 0.095 | None | 0.237 | 0.027 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 7.68935E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/M | rs375807609 |
-0.471 | 0.095 | None | 0.237 | 0.027 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| V/M | rs375807609 |
-0.471 | 0.095 | None | 0.237 | 0.027 | None | gnomAD-4.0.0 | 5.20488E-05 | None | None | None | None | N | None | 6.66311E-05 | 9.999E-05 | None | 0 | 5.34688E-04 | None | 0 | 0 | 3.5599E-05 | 5.48992E-05 | 3.20102E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2621 | likely_benign | 0.2212 | benign | -2.036 | Highly Destabilizing | 0.165 | N | 0.456 | neutral | None | None | None | None | N |
| V/C | 0.7561 | likely_pathogenic | 0.7436 | pathogenic | -1.384 | Destabilizing | 0.932 | D | 0.691 | prob.neutral | None | None | None | None | N |
| V/D | 0.9088 | likely_pathogenic | 0.8549 | pathogenic | -2.829 | Highly Destabilizing | 0.932 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/E | 0.789 | likely_pathogenic | 0.6807 | pathogenic | -2.604 | Highly Destabilizing | 0.492 | N | 0.703 | prob.neutral | None | None | None | None | N |
| V/F | 0.2489 | likely_benign | 0.2065 | benign | -1.249 | Destabilizing | 0.241 | N | 0.679 | prob.neutral | None | None | None | None | N |
| V/G | 0.4489 | ambiguous | 0.3678 | ambiguous | -2.548 | Highly Destabilizing | 0.492 | N | 0.701 | prob.neutral | None | None | None | None | N |
| V/H | 0.871 | likely_pathogenic | 0.8195 | pathogenic | -2.237 | Highly Destabilizing | 0.981 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/I | 0.0772 | likely_benign | 0.0787 | benign | -0.604 | Destabilizing | 0.054 | N | 0.401 | neutral | None | None | None | None | N |
| V/K | 0.7737 | likely_pathogenic | 0.6599 | pathogenic | -1.931 | Destabilizing | 0.388 | N | 0.668 | neutral | None | None | None | None | N |
| V/L | 0.0937 | likely_benign | 0.0841 | benign | -0.604 | Destabilizing | 0.001 | N | 0.149 | neutral | None | None | None | None | N |
| V/M | 0.1385 | likely_benign | 0.1065 | benign | -0.491 | Destabilizing | 0.095 | N | 0.237 | neutral | None | None | None | None | N |
| V/N | 0.805 | likely_pathogenic | 0.7366 | pathogenic | -2.28 | Highly Destabilizing | 0.818 | D | 0.736 | prob.delet. | None | None | None | None | N |
| V/P | 0.9218 | likely_pathogenic | 0.8769 | pathogenic | -1.056 | Destabilizing | 0.932 | D | 0.703 | prob.neutral | None | None | None | None | N |
| V/Q | 0.6933 | likely_pathogenic | 0.5814 | pathogenic | -2.14 | Highly Destabilizing | 0.818 | D | 0.705 | prob.neutral | None | None | None | None | N |
| V/R | 0.6887 | likely_pathogenic | 0.5702 | pathogenic | -1.693 | Destabilizing | 0.818 | D | 0.731 | prob.delet. | None | None | None | None | N |
| V/S | 0.5188 | ambiguous | 0.4357 | ambiguous | -2.82 | Highly Destabilizing | 0.563 | D | 0.627 | neutral | None | None | None | None | N |
| V/T | 0.3675 | ambiguous | 0.2976 | benign | -2.46 | Highly Destabilizing | 0.388 | N | 0.561 | neutral | None | None | None | None | N |
| V/W | 0.8921 | likely_pathogenic | 0.8234 | pathogenic | -1.789 | Destabilizing | 0.981 | D | 0.706 | prob.neutral | None | None | None | None | N |
| V/Y | 0.7786 | likely_pathogenic | 0.7155 | pathogenic | -1.372 | Destabilizing | 0.818 | D | 0.717 | prob.delet. | 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.