Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15347 | 46264;46265;46266 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| N2AB | 13706 | 41341;41342;41343 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| N2A | 12779 | 38560;38561;38562 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| N2B | 6282 | 19069;19070;19071 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| Novex-1 | 6407 | 19444;19445;19446 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| Novex-2 | 6474 | 19645;19646;19647 | chr2:178620482;178620481;178620480 | chr2:179485209;179485208;179485207 |
| 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 | 0.611 | 0.276 | 0.676464442291 | gnomAD-4.0.0 | 2.05422E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.48004E-05 | 0 |
| V/G | rs375367475  |
-2.695 | 0.667 | N | 0.748 | 0.491 | None | gnomAD-2.1.1 | 6.45E-05 | None | None | None | None | N | None | 7.4491E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/G | rs375367475 |
-2.695 | 0.667 | N | 0.748 | 0.491 | None | gnomAD-3.1.2 | 2.30427E-04 | None | None | None | None | N | None | 8.21296E-04 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/G | rs375367475 |
-2.695 | 0.667 | N | 0.748 | 0.491 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/G | rs375367475 |
-2.695 | 0.667 | N | 0.748 | 0.491 | None | gnomAD-4.0.0 | 3.41103E-05 | None | None | None | None | N | None | 6.94166E-04 | 1.67006E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20461E-05 |
| V/I | None | None | None | N | 0.166 | 0.111 | 0.278968121808 | gnomAD-4.0.0 | 1.36948E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00022E-07 | 0 | 1.65843E-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 | 0.471 | ambiguous | 0.4771 | ambiguous | -1.997 | Destabilizing | 0.104 | N | 0.611 | neutral | N | 0.515252489 | None | None | N |
| V/C | 0.6882 | likely_pathogenic | 0.7707 | pathogenic | -1.647 | Destabilizing | 0.968 | D | 0.674 | neutral | None | None | None | None | N |
| V/D | 0.8459 | likely_pathogenic | 0.8522 | pathogenic | -2.473 | Highly Destabilizing | 0.667 | D | 0.797 | deleterious | D | 0.547590697 | None | None | N |
| V/E | 0.7213 | likely_pathogenic | 0.7405 | pathogenic | -2.335 | Highly Destabilizing | 0.726 | D | 0.714 | prob.delet. | None | None | None | None | N |
| V/F | 0.2034 | likely_benign | 0.2363 | benign | -1.312 | Destabilizing | 0.497 | N | 0.685 | prob.neutral | N | 0.473900731 | None | None | N |
| V/G | 0.5301 | ambiguous | 0.3957 | ambiguous | -2.467 | Highly Destabilizing | 0.667 | D | 0.748 | deleterious | N | 0.515546359 | None | None | N |
| V/H | 0.7605 | likely_pathogenic | 0.8142 | pathogenic | -2.185 | Highly Destabilizing | 0.968 | D | 0.778 | deleterious | None | None | None | None | N |
| V/I | 0.0716 | likely_benign | 0.0751 | benign | -0.728 | Destabilizing | None | N | 0.166 | neutral | N | 0.411079096 | None | None | N |
| V/K | 0.673 | likely_pathogenic | 0.6777 | pathogenic | -1.737 | Destabilizing | 0.726 | D | 0.702 | prob.neutral | None | None | None | None | N |
| V/L | 0.2129 | likely_benign | 0.2384 | benign | -0.728 | Destabilizing | None | N | 0.174 | neutral | N | 0.478014331 | None | None | N |
| V/M | 0.2356 | likely_benign | 0.2688 | benign | -0.731 | Destabilizing | 0.567 | D | 0.667 | neutral | None | None | None | None | N |
| V/N | 0.6286 | likely_pathogenic | 0.6502 | pathogenic | -1.858 | Destabilizing | 0.89 | D | 0.791 | deleterious | None | None | None | None | N |
| V/P | 0.9469 | likely_pathogenic | 0.9559 | pathogenic | -1.121 | Destabilizing | 0.89 | D | 0.732 | prob.delet. | None | None | None | None | N |
| V/Q | 0.6436 | likely_pathogenic | 0.6696 | pathogenic | -1.832 | Destabilizing | 0.89 | D | 0.72 | prob.delet. | None | None | None | None | N |
| V/R | 0.5749 | likely_pathogenic | 0.5786 | pathogenic | -1.41 | Destabilizing | 0.726 | D | 0.795 | deleterious | None | None | None | None | N |
| V/S | 0.5569 | ambiguous | 0.5732 | pathogenic | -2.452 | Highly Destabilizing | 0.726 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/T | 0.4151 | ambiguous | 0.4396 | ambiguous | -2.184 | Highly Destabilizing | 0.272 | N | 0.618 | neutral | None | None | None | None | N |
| V/W | 0.8372 | likely_pathogenic | 0.8941 | pathogenic | -1.753 | Destabilizing | 0.968 | D | 0.789 | deleterious | None | None | None | None | N |
| V/Y | 0.5321 | ambiguous | 0.637 | pathogenic | -1.401 | Destabilizing | 0.726 | 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.