Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31794 | 95605;95606;95607 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| N2AB | 30153 | 90682;90683;90684 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| N2A | 29226 | 87901;87902;87903 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| N2B | 22729 | 68410;68411;68412 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| Novex-1 | 22854 | 68785;68786;68787 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| Novex-2 | 22921 | 68986;68987;68988 | chr2:178545856;178545855;178545854 | chr2:179410583;179410582;179410581 |
| 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 | rs2154145428  |
None | None | N | 0.252 | 0.129 | 0.132336055621 | gnomAD-4.0.0 | 3.18273E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.546E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs1346238621 |
-0.538 | None | N | 0.182 | 0.085 | 0.115124310173 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0808 | likely_benign | 0.0825 | benign | -1.527 | Destabilizing | None | N | 0.252 | neutral | N | 0.40778817 | None | None | N |
| V/C | 0.4006 | ambiguous | 0.387 | ambiguous | -1.069 | Destabilizing | 0.366 | N | 0.511 | neutral | None | None | None | None | N |
| V/D | 0.2672 | likely_benign | 0.2786 | benign | -1.265 | Destabilizing | 0.303 | N | 0.659 | prob.neutral | N | 0.484344798 | None | None | N |
| V/E | 0.1744 | likely_benign | 0.1802 | benign | -1.247 | Destabilizing | 0.075 | N | 0.534 | neutral | None | None | None | None | N |
| V/F | 0.1582 | likely_benign | 0.1516 | benign | -1.071 | Destabilizing | 0.058 | N | 0.574 | neutral | N | 0.495292511 | None | None | N |
| V/G | 0.1391 | likely_benign | 0.15 | benign | -1.867 | Destabilizing | 0.03 | N | 0.625 | neutral | N | 0.429952953 | None | None | N |
| V/H | 0.3745 | ambiguous | 0.3734 | ambiguous | -1.406 | Destabilizing | 0.869 | D | 0.709 | prob.delet. | None | None | None | None | N |
| V/I | 0.0724 | likely_benign | 0.0693 | benign | -0.686 | Destabilizing | None | N | 0.228 | neutral | N | 0.442690177 | None | None | N |
| V/K | 0.235 | likely_benign | 0.2381 | benign | -1.319 | Destabilizing | 0.075 | N | 0.514 | neutral | None | None | None | None | N |
| V/L | 0.0875 | likely_benign | 0.0862 | benign | -0.686 | Destabilizing | None | N | 0.182 | neutral | N | 0.305509164 | None | None | N |
| V/M | 0.0843 | likely_benign | 0.0825 | benign | -0.598 | Destabilizing | 0.221 | N | 0.501 | neutral | None | None | None | None | N |
| V/N | 0.1828 | likely_benign | 0.1767 | benign | -1.113 | Destabilizing | 0.366 | N | 0.667 | prob.neutral | None | None | None | None | N |
| V/P | 0.7897 | likely_pathogenic | 0.7534 | pathogenic | -0.932 | Destabilizing | 0.366 | N | 0.527 | neutral | None | None | None | None | N |
| V/Q | 0.1785 | likely_benign | 0.1846 | benign | -1.25 | Destabilizing | 0.366 | N | 0.531 | neutral | None | None | None | None | N |
| V/R | 0.1975 | likely_benign | 0.2076 | benign | -0.843 | Destabilizing | 0.221 | N | 0.671 | prob.neutral | None | None | None | None | N |
| V/S | 0.1121 | likely_benign | 0.1126 | benign | -1.664 | Destabilizing | 0.039 | N | 0.563 | neutral | None | None | None | None | N |
| V/T | 0.086 | likely_benign | 0.0848 | benign | -1.535 | Destabilizing | 0.075 | N | 0.455 | neutral | None | None | None | None | N |
| V/W | 0.6171 | likely_pathogenic | 0.6266 | pathogenic | -1.268 | Destabilizing | 0.869 | D | 0.744 | deleterious | None | None | None | None | N |
| V/Y | 0.3813 | ambiguous | 0.3882 | ambiguous | -0.985 | Destabilizing | 0.366 | N | 0.569 | 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.