Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20274 | 61045;61046;61047 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| N2AB | 18633 | 56122;56123;56124 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| N2A | 17706 | 53341;53342;53343 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| N2B | 11209 | 33850;33851;33852 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| Novex-1 | 11334 | 34225;34226;34227 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| Novex-2 | 11401 | 34426;34427;34428 | chr2:178590905;178590904;178590903 | chr2:179455632;179455631;179455630 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs72646845  |
-0.851 | 0.997 | N | 0.813 | 0.39 | None | gnomAD-2.1.1 | 3.34794E-03 | None | None | None | None | I | None | 2.48077E-04 | 8.50003E-04 | None | 1.68801E-02 | 0 | None | 1.74784E-02 | None | 1.20298E-04 | 1.27875E-03 | 3.5251E-03 |
| P/L | rs72646845 |
-0.851 | 0.997 | N | 0.813 | 0.39 | None | gnomAD-3.1.2 | 1.38743E-03 | None | None | None | None | I | None | 1.44774E-04 | 5.90087E-04 | 2.19298E-03 | 1.35525E-02 | 0 | None | 4.70633E-04 | 0 | 9.41315E-04 | 1.59552E-02 | 4.78469E-04 |
| P/L | rs72646845 |
-0.851 | 0.997 | N | 0.813 | 0.39 | None | 1000 genomes | 2.99521E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 0 | None | None | None | 1.53E-02 | None |
| P/L | rs72646845 |
-0.851 | 0.997 | N | 0.813 | 0.39 | None | gnomAD-4.0.0 | 2.03316E-03 | None | None | None | None | I | None | 2E-04 | 8.17348E-04 | None | 1.65393E-02 | 0 | None | 9.37588E-05 | 1.17511E-02 | 8.11115E-04 | 1.68223E-02 | 2.54718E-03 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0612 | likely_benign | 0.0599 | benign | -1.414 | Destabilizing | 0.978 | D | 0.754 | deleterious | N | 0.454003249 | None | None | I |
| P/C | 0.3698 | ambiguous | 0.3122 | benign | -1.121 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | I |
| P/D | 0.6751 | likely_pathogenic | 0.6175 | pathogenic | -1.474 | Destabilizing | 0.998 | D | 0.793 | deleterious | None | None | None | None | I |
| P/E | 0.2882 | likely_benign | 0.2496 | benign | -1.518 | Destabilizing | 0.967 | D | 0.774 | deleterious | None | None | None | None | I |
| P/F | 0.5124 | ambiguous | 0.467 | ambiguous | -1.364 | Destabilizing | 0.999 | D | 0.841 | deleterious | None | None | None | None | I |
| P/G | 0.4612 | ambiguous | 0.4127 | ambiguous | -1.669 | Destabilizing | 0.998 | D | 0.813 | deleterious | None | None | None | None | I |
| P/H | 0.2384 | likely_benign | 0.2133 | benign | -1.175 | Destabilizing | 0.421 | N | 0.66 | neutral | N | 0.494276114 | None | None | I |
| P/I | 0.3154 | likely_benign | 0.2909 | benign | -0.829 | Destabilizing | 0.999 | D | 0.835 | deleterious | None | None | None | None | I |
| P/K | 0.4274 | ambiguous | 0.3771 | ambiguous | -1.041 | Destabilizing | 0.967 | D | 0.786 | deleterious | None | None | None | None | I |
| P/L | 0.1707 | likely_benign | 0.1713 | benign | -0.829 | Destabilizing | 0.997 | D | 0.813 | deleterious | N | 0.52052067 | None | None | I |
| P/M | 0.3285 | likely_benign | 0.2897 | benign | -0.616 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | I |
| P/N | 0.5131 | ambiguous | 0.4495 | ambiguous | -0.838 | Destabilizing | 0.995 | D | 0.831 | deleterious | None | None | None | None | I |
| P/Q | 0.1738 | likely_benign | 0.1506 | benign | -1.123 | Destabilizing | 0.84 | D | 0.617 | neutral | None | None | None | None | I |
| P/R | 0.2753 | likely_benign | 0.2444 | benign | -0.486 | Destabilizing | 0.994 | D | 0.833 | deleterious | N | 0.485019722 | None | None | I |
| P/S | 0.1218 | likely_benign | 0.1125 | benign | -1.319 | Destabilizing | 0.978 | D | 0.787 | deleterious | N | 0.471915444 | None | None | I |
| P/T | 0.1444 | likely_benign | 0.1362 | benign | -1.263 | Destabilizing | 0.997 | D | 0.784 | deleterious | N | 0.493515645 | None | None | I |
| P/V | 0.2108 | likely_benign | 0.1985 | benign | -0.99 | Destabilizing | 0.998 | D | 0.829 | deleterious | None | None | None | None | I |
| P/W | 0.7546 | likely_pathogenic | 0.7091 | pathogenic | -1.462 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | I |
| P/Y | 0.5104 | ambiguous | 0.4577 | ambiguous | -1.165 | Destabilizing | 0.995 | D | 0.851 | deleterious | None | None | None | None | I |
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.