Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30235 | 90928;90929;90930 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| N2AB | 28594 | 86005;86006;86007 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| N2A | 27667 | 83224;83225;83226 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| N2B | 21170 | 63733;63734;63735 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| Novex-1 | 21295 | 64108;64109;64110 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| Novex-2 | 21362 | 64309;64310;64311 | chr2:178552197;178552196;178552195 | chr2:179416924;179416923;179416922 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs753966975  |
-0.206 | 0.006 | N | 0.246 | 0.047 | 0.107399877778 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/E | rs753966975 |
-0.206 | 0.006 | N | 0.246 | 0.047 | 0.107399877778 | gnomAD-4.0.0 | 4.1057E-06 | None | None | None | None | N | None | 0 | 2.23714E-05 | None | 0 | 0 | None | 0 | 0 | 4.49754E-06 | 0 | 0 |
| D/N | rs1172858203 |
-0.451 | 0.645 | N | 0.526 | 0.3 | 0.213573922156 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| D/N | rs1172858203 |
-0.451 | 0.645 | N | 0.526 | 0.3 | 0.213573922156 | gnomAD-4.0.0 | 2.05289E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69857E-06 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2915 | likely_benign | 0.3545 | ambiguous | -0.352 | Destabilizing | 0.477 | N | 0.568 | neutral | D | 0.52221254 | None | None | N |
| D/C | 0.7247 | likely_pathogenic | 0.7938 | pathogenic | -0.149 | Destabilizing | 0.995 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/E | 0.152 | likely_benign | 0.2116 | benign | -0.266 | Destabilizing | 0.006 | N | 0.246 | neutral | N | 0.45787306 | None | None | N |
| D/F | 0.787 | likely_pathogenic | 0.8287 | pathogenic | -0.038 | Destabilizing | 0.945 | D | 0.74 | deleterious | None | None | None | None | N |
| D/G | 0.3462 | ambiguous | 0.3891 | ambiguous | -0.588 | Destabilizing | 0.645 | D | 0.595 | neutral | N | 0.521559179 | None | None | N |
| D/H | 0.408 | ambiguous | 0.4521 | ambiguous | 0.172 | Stabilizing | 0.029 | N | 0.358 | neutral | N | 0.471786858 | None | None | N |
| D/I | 0.4794 | ambiguous | 0.593 | pathogenic | 0.236 | Stabilizing | 0.945 | D | 0.753 | deleterious | None | None | None | None | N |
| D/K | 0.5353 | ambiguous | 0.5924 | pathogenic | 0.274 | Stabilizing | 0.809 | D | 0.652 | neutral | None | None | None | None | N |
| D/L | 0.4923 | ambiguous | 0.5882 | pathogenic | 0.236 | Stabilizing | 0.894 | D | 0.753 | deleterious | None | None | None | None | N |
| D/M | 0.6849 | likely_pathogenic | 0.7778 | pathogenic | 0.292 | Stabilizing | 0.995 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/N | 0.1548 | likely_benign | 0.1843 | benign | -0.237 | Destabilizing | 0.645 | D | 0.526 | neutral | N | 0.473913225 | None | None | N |
| D/P | 0.9297 | likely_pathogenic | 0.9526 | pathogenic | 0.063 | Stabilizing | 0.945 | D | 0.715 | prob.delet. | None | None | None | None | N |
| D/Q | 0.4082 | ambiguous | 0.4858 | ambiguous | -0.162 | Destabilizing | 0.809 | D | 0.621 | neutral | None | None | None | None | N |
| D/R | 0.5935 | likely_pathogenic | 0.6226 | pathogenic | 0.534 | Stabilizing | 0.894 | D | 0.731 | prob.delet. | None | None | None | None | N |
| D/S | 0.181 | likely_benign | 0.2078 | benign | -0.343 | Destabilizing | 0.547 | D | 0.536 | neutral | None | None | None | None | N |
| D/T | 0.2836 | likely_benign | 0.3462 | ambiguous | -0.146 | Destabilizing | 0.894 | D | 0.617 | neutral | None | None | None | None | N |
| D/V | 0.3154 | likely_benign | 0.403 | ambiguous | 0.063 | Stabilizing | 0.864 | D | 0.754 | deleterious | N | 0.498874321 | None | None | N |
| D/W | 0.9317 | likely_pathogenic | 0.9429 | pathogenic | 0.172 | Stabilizing | 0.995 | D | 0.706 | prob.neutral | None | None | None | None | N |
| D/Y | 0.4285 | ambiguous | 0.4776 | ambiguous | 0.219 | Stabilizing | 0.864 | D | 0.756 | deleterious | N | 0.474673694 | 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.