Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18316 | 55171;55172;55173 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| N2AB | 16675 | 50248;50249;50250 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| N2A | 15748 | 47467;47468;47469 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| N2B | 9251 | 27976;27977;27978 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| Novex-1 | 9376 | 28351;28352;28353 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| Novex-2 | 9443 | 28552;28553;28554 | chr2:178602456;178602455;178602454 | chr2:179467183;179467182;179467181 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | None | None | 0.317 | N | 0.293 | 0.068 | 0.132336055621 | gnomAD-4.0.0 | 1.59429E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86298E-06 | 0 | 0 |
| T/S | rs758527900  |
-0.297 | None | N | 0.082 | 0.072 | 0.0401082797425 | gnomAD-2.1.1 | 7.46968E-04 | None | None | None | None | N | None | 0 | 5.32782E-03 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.34001E-04 |
| T/S | rs758527900 |
-0.297 | None | N | 0.082 | 0.072 | 0.0401082797425 | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 0 | 4.59318E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/S | rs758527900 |
-0.297 | None | N | 0.082 | 0.072 | 0.0401082797425 | gnomAD-4.0.0 | 2.70801E-04 | None | None | None | None | N | None | 0 | 3.49888E-03 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.42507E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0871 | likely_benign | 0.0829 | benign | -0.346 | Destabilizing | 0.012 | N | 0.197 | neutral | N | 0.409244033 | None | None | N |
| T/C | 0.2788 | likely_benign | 0.2643 | benign | -0.126 | Destabilizing | 0.824 | D | 0.247 | neutral | None | None | None | None | N |
| T/D | 0.3094 | likely_benign | 0.2584 | benign | -0.095 | Destabilizing | 0.081 | N | 0.255 | neutral | None | None | None | None | N |
| T/E | 0.2995 | likely_benign | 0.2642 | benign | -0.187 | Destabilizing | 0.081 | N | 0.257 | neutral | None | None | None | None | N |
| T/F | 0.2881 | likely_benign | 0.276 | benign | -0.901 | Destabilizing | 0.555 | D | 0.33 | neutral | None | None | None | None | N |
| T/G | 0.1499 | likely_benign | 0.1254 | benign | -0.454 | Destabilizing | None | N | 0.144 | neutral | None | None | None | None | N |
| T/H | 0.2834 | likely_benign | 0.2624 | benign | -0.841 | Destabilizing | 0.555 | D | 0.313 | neutral | None | None | None | None | N |
| T/I | 0.2876 | likely_benign | 0.2707 | benign | -0.18 | Destabilizing | 0.317 | N | 0.293 | neutral | N | 0.453263032 | None | None | N |
| T/K | 0.2374 | likely_benign | 0.2197 | benign | -0.337 | Destabilizing | 0.002 | N | 0.205 | neutral | None | None | None | None | N |
| T/L | 0.1401 | likely_benign | 0.1272 | benign | -0.18 | Destabilizing | 0.149 | N | 0.267 | neutral | None | None | None | None | N |
| T/M | 0.1186 | likely_benign | 0.1114 | benign | 0.154 | Stabilizing | 0.791 | D | 0.243 | neutral | None | None | None | None | N |
| T/N | 0.1084 | likely_benign | 0.1051 | benign | -0.049 | Destabilizing | 0.062 | N | 0.25 | neutral | N | 0.424250771 | None | None | N |
| T/P | 0.395 | ambiguous | 0.4162 | ambiguous | -0.208 | Destabilizing | 0.317 | N | 0.31 | neutral | N | 0.439393582 | None | None | N |
| T/Q | 0.2274 | likely_benign | 0.2097 | benign | -0.36 | Destabilizing | 0.38 | N | 0.301 | neutral | None | None | None | None | N |
| T/R | 0.2131 | likely_benign | 0.2198 | benign | -0.035 | Destabilizing | 0.081 | N | 0.287 | neutral | None | None | None | None | N |
| T/S | 0.0793 | likely_benign | 0.0747 | benign | -0.22 | Destabilizing | None | N | 0.082 | neutral | N | 0.393175716 | None | None | N |
| T/V | 0.2009 | likely_benign | 0.1885 | benign | -0.208 | Destabilizing | 0.149 | N | 0.245 | neutral | None | None | None | None | N |
| T/W | 0.5767 | likely_pathogenic | 0.5714 | pathogenic | -0.9 | Destabilizing | 0.935 | D | 0.375 | neutral | None | None | None | None | N |
| T/Y | 0.2985 | likely_benign | 0.2812 | benign | -0.618 | Destabilizing | 0.555 | D | 0.327 | 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.