Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18108 | 54547;54548;54549 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| N2AB | 16467 | 49624;49625;49626 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| N2A | 15540 | 46843;46844;46845 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| N2B | 9043 | 27352;27353;27354 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| Novex-1 | 9168 | 27727;27728;27729 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| Novex-2 | 9235 | 27928;27929;27930 | chr2:178604767;178604766;178604765 | chr2:179469494;179469493;179469492 |
| 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/R | rs1460827160  |
None | 0.015 | N | 0.201 | 0.145 | 0.124217242631 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/R | rs1460827160 |
None | 0.015 | N | 0.201 | 0.145 | 0.124217242631 | gnomAD-4.0.0 | 1.86085E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.5447E-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 | 0.0908 | likely_benign | 0.1023 | benign | -0.252 | Destabilizing | 0.863 | D | 0.208 | neutral | None | None | None | None | N |
| S/C | 0.2151 | likely_benign | 0.2532 | benign | -0.237 | Destabilizing | 0.999 | D | 0.265 | neutral | N | 0.494374565 | None | None | N |
| S/D | 0.4888 | ambiguous | 0.6131 | pathogenic | -0.051 | Destabilizing | 0.969 | D | 0.183 | neutral | None | None | None | None | N |
| S/E | 0.5529 | ambiguous | 0.6639 | pathogenic | -0.164 | Destabilizing | 0.863 | D | 0.229 | neutral | None | None | None | None | N |
| S/F | 0.319 | likely_benign | 0.3975 | ambiguous | -0.915 | Destabilizing | 0.997 | D | 0.309 | neutral | None | None | None | None | N |
| S/G | 0.0935 | likely_benign | 0.1138 | benign | -0.324 | Destabilizing | 0.906 | D | 0.226 | neutral | N | 0.483960796 | None | None | N |
| S/H | 0.4463 | ambiguous | 0.5485 | ambiguous | -0.759 | Destabilizing | 0.997 | D | 0.214 | neutral | None | None | None | None | N |
| S/I | 0.2761 | likely_benign | 0.3802 | ambiguous | -0.195 | Destabilizing | 0.996 | D | 0.328 | neutral | N | 0.467623029 | None | None | N |
| S/K | 0.6887 | likely_pathogenic | 0.8047 | pathogenic | -0.438 | Destabilizing | 0.079 | N | 0.117 | neutral | None | None | None | None | N |
| S/L | 0.1403 | likely_benign | 0.1645 | benign | -0.195 | Destabilizing | 0.969 | D | 0.285 | neutral | None | None | None | None | N |
| S/M | 0.2697 | likely_benign | 0.3267 | benign | 0.039 | Stabilizing | 0.997 | D | 0.216 | neutral | None | None | None | None | N |
| S/N | 0.164 | likely_benign | 0.2361 | benign | -0.107 | Destabilizing | 0.959 | D | 0.219 | neutral | N | 0.509992604 | None | None | N |
| S/P | 0.6305 | likely_pathogenic | 0.7283 | pathogenic | -0.188 | Destabilizing | 0.997 | D | 0.211 | neutral | None | None | None | None | N |
| S/Q | 0.4924 | ambiguous | 0.5983 | pathogenic | -0.41 | Destabilizing | 0.939 | D | 0.207 | neutral | None | None | None | None | N |
| S/R | 0.6185 | likely_pathogenic | 0.7379 | pathogenic | -0.153 | Destabilizing | 0.015 | N | 0.201 | neutral | N | 0.476864253 | None | None | N |
| S/T | 0.0832 | likely_benign | 0.0897 | benign | -0.233 | Destabilizing | 0.959 | D | 0.237 | neutral | N | 0.489428118 | None | None | N |
| S/V | 0.2266 | likely_benign | 0.3034 | benign | -0.188 | Destabilizing | 0.969 | D | 0.291 | neutral | None | None | None | None | N |
| S/W | 0.5207 | ambiguous | 0.5867 | pathogenic | -0.943 | Destabilizing | 0.999 | D | 0.43 | neutral | None | None | None | None | N |
| S/Y | 0.3138 | likely_benign | 0.4048 | ambiguous | -0.656 | Destabilizing | 0.997 | D | 0.311 | 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.