Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23065 | 69418;69419;69420 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| N2AB | 21424 | 64495;64496;64497 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| N2A | 20497 | 61714;61715;61716 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| N2B | 14000 | 42223;42224;42225 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| Novex-1 | 14125 | 42598;42599;42600 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| Novex-2 | 14192 | 42799;42800;42801 | chr2:178577142;178577141;178577140 | chr2:179441869;179441868;179441867 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs768535148  |
-0.124 | 0.166 | N | 0.306 | 0.11 | 0.493021045079 | gnomAD-2.1.1 | 8.95E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.29306E-03 | None | 0 | None | 0 | 0 | 0 |
| L/S | rs768535148 |
-0.124 | 0.166 | N | 0.306 | 0.11 | 0.493021045079 | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.3587E-03 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs768535148 |
-0.124 | 0.166 | N | 0.306 | 0.11 | 0.493021045079 | gnomAD-4.0.0 | 5.26964E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.83404E-03 | None | 0 | 0 | 0 | 1.09832E-05 | 3.20379E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.0846 | likely_benign | 0.0869 | benign | -0.4 | Destabilizing | 0.001 | N | 0.121 | neutral | None | None | None | None | I |
| L/C | 0.3515 | ambiguous | 0.3604 | ambiguous | -0.679 | Destabilizing | 0.901 | D | 0.258 | neutral | None | None | None | None | I |
| L/D | 0.3112 | likely_benign | 0.2947 | benign | -0.1 | Destabilizing | 0.39 | N | 0.395 | neutral | None | None | None | None | I |
| L/E | 0.1396 | likely_benign | 0.1284 | benign | -0.202 | Destabilizing | 0.007 | N | 0.177 | neutral | None | None | None | None | I |
| L/F | 0.1216 | likely_benign | 0.1277 | benign | -0.54 | Destabilizing | 0.003 | N | 0.179 | neutral | N | 0.48509172 | None | None | I |
| L/G | 0.2323 | likely_benign | 0.2457 | benign | -0.515 | Destabilizing | 0.209 | N | 0.321 | neutral | None | None | None | None | I |
| L/H | 0.1303 | likely_benign | 0.1357 | benign | 0.1 | Stabilizing | 0.965 | D | 0.238 | neutral | None | None | None | None | I |
| L/I | 0.0816 | likely_benign | 0.0789 | benign | -0.228 | Destabilizing | 0.083 | N | 0.335 | neutral | None | None | None | None | I |
| L/K | 0.1178 | likely_benign | 0.104 | benign | -0.231 | Destabilizing | 0.561 | D | 0.343 | neutral | None | None | None | None | I |
| L/M | 0.0826 | likely_benign | 0.0876 | benign | -0.427 | Destabilizing | 0.873 | D | 0.279 | neutral | N | 0.470229922 | None | None | I |
| L/N | 0.172 | likely_benign | 0.163 | benign | -0.066 | Destabilizing | 0.901 | D | 0.334 | neutral | None | None | None | None | I |
| L/P | 0.1648 | likely_benign | 0.1488 | benign | -0.255 | Destabilizing | 0.901 | D | 0.341 | neutral | None | None | None | None | I |
| L/Q | 0.0766 | likely_benign | 0.0722 | benign | -0.273 | Destabilizing | 0.561 | D | 0.365 | neutral | None | None | None | None | I |
| L/R | 0.1115 | likely_benign | 0.1068 | benign | 0.254 | Stabilizing | 0.561 | D | 0.362 | neutral | None | None | None | None | I |
| L/S | 0.1097 | likely_benign | 0.108 | benign | -0.469 | Destabilizing | 0.166 | N | 0.306 | neutral | N | 0.473669232 | None | None | I |
| L/T | 0.0915 | likely_benign | 0.0964 | benign | -0.467 | Destabilizing | 0.345 | N | 0.311 | neutral | None | None | None | None | I |
| L/V | 0.0716 | likely_benign | 0.0734 | benign | -0.255 | Destabilizing | 0.001 | N | 0.112 | neutral | N | 0.482694147 | None | None | I |
| L/W | 0.2177 | likely_benign | 0.2248 | benign | -0.56 | Destabilizing | 0.987 | D | 0.25 | neutral | N | 0.493196023 | None | None | I |
| L/Y | 0.2439 | likely_benign | 0.2502 | benign | -0.305 | Destabilizing | 0.39 | N | 0.344 | neutral | 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.