Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26412 | 79459;79460;79461 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| N2AB | 24771 | 74536;74537;74538 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| N2A | 23844 | 71755;71756;71757 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| N2B | 17347 | 52264;52265;52266 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| Novex-1 | 17472 | 52639;52640;52641 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| Novex-2 | 17539 | 52840;52841;52842 | chr2:178566898;178566897;178566896 | chr2:179431625;179431624;179431623 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.101 | N | 0.265 | 0.086 | 0.162503812791 | gnomAD-4.0.0 | 1.36859E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 3.46741E-04 | 0 | 0 | 0 |
| S/N | rs752040235  |
0.076 | 0.002 | N | 0.139 | 0.048 | 0.141422826196 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.64E-05 | 0 | 0 |
| S/N | rs752040235 |
0.076 | 0.002 | N | 0.139 | 0.048 | 0.141422826196 | gnomAD-4.0.0 | 3.42143E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.87322E-05 | 0 | 3.59817E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0888 | likely_benign | 0.0955 | benign | -0.428 | Destabilizing | 0.004 | N | 0.055 | neutral | None | None | None | None | I |
| S/C | 0.1039 | likely_benign | 0.1134 | benign | -0.24 | Destabilizing | 0.978 | D | 0.36 | neutral | N | 0.480595042 | None | None | I |
| S/D | 0.288 | likely_benign | 0.2846 | benign | -0.088 | Destabilizing | 0.264 | N | 0.233 | neutral | None | None | None | None | I |
| S/E | 0.4763 | ambiguous | 0.4974 | ambiguous | -0.191 | Destabilizing | 0.418 | N | 0.22 | neutral | None | None | None | None | I |
| S/F | 0.1681 | likely_benign | 0.1963 | benign | -1.082 | Destabilizing | 0.557 | D | 0.485 | neutral | None | None | None | None | I |
| S/G | 0.11 | likely_benign | 0.1183 | benign | -0.522 | Destabilizing | 0.101 | N | 0.265 | neutral | N | 0.467326179 | None | None | I |
| S/H | 0.2946 | likely_benign | 0.3043 | benign | -1.089 | Destabilizing | 0.005 | N | 0.219 | neutral | None | None | None | None | I |
| S/I | 0.1594 | likely_benign | 0.1887 | benign | -0.308 | Destabilizing | 0.351 | N | 0.491 | neutral | N | 0.47744149 | None | None | I |
| S/K | 0.639 | likely_pathogenic | 0.6733 | pathogenic | -0.509 | Destabilizing | 0.418 | N | 0.217 | neutral | None | None | None | None | I |
| S/L | 0.0979 | likely_benign | 0.1098 | benign | -0.308 | Destabilizing | 0.129 | N | 0.404 | neutral | None | None | None | None | I |
| S/M | 0.1628 | likely_benign | 0.1748 | benign | 0.073 | Stabilizing | 0.94 | D | 0.372 | neutral | None | None | None | None | I |
| S/N | 0.1067 | likely_benign | 0.1095 | benign | -0.214 | Destabilizing | 0.002 | N | 0.139 | neutral | N | 0.45569676 | None | None | I |
| S/P | 0.8458 | likely_pathogenic | 0.8293 | pathogenic | -0.321 | Destabilizing | 0.94 | D | 0.455 | neutral | None | None | None | None | I |
| S/Q | 0.4581 | ambiguous | 0.4851 | ambiguous | -0.517 | Destabilizing | 0.716 | D | 0.345 | neutral | None | None | None | None | I |
| S/R | 0.5769 | likely_pathogenic | 0.6116 | pathogenic | -0.274 | Destabilizing | 0.351 | N | 0.434 | neutral | N | 0.51853473 | None | None | I |
| S/T | 0.072 | likely_benign | 0.0725 | benign | -0.311 | Destabilizing | 0.003 | N | 0.062 | neutral | N | 0.468068624 | None | None | I |
| S/V | 0.1476 | likely_benign | 0.1657 | benign | -0.321 | Destabilizing | 0.418 | N | 0.402 | neutral | None | None | None | None | I |
| S/W | 0.3964 | ambiguous | 0.4281 | ambiguous | -1.08 | Destabilizing | 0.951 | D | 0.421 | neutral | None | None | None | None | I |
| S/Y | 0.1835 | likely_benign | 0.1954 | benign | -0.804 | Destabilizing | 0.002 | N | 0.259 | 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.