Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22409 | 67450;67451;67452 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| N2AB | 20768 | 62527;62528;62529 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| N2A | 19841 | 59746;59747;59748 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| N2B | 13344 | 40255;40256;40257 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| Novex-1 | 13469 | 40630;40631;40632 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| Novex-2 | 13536 | 40831;40832;40833 | chr2:178580062;178580061;178580060 | chr2:179444789;179444788;179444787 |
| 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/C | None | None | None | N | 0.14 | 0.321 | 0.317084106153 | gnomAD-4.0.0 | 1.5922E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| S/F | rs1296710770  |
-0.812 | 0.56 | N | 0.302 | 0.272 | 0.520427616228 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.98965E-04 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/F | rs1296710770 |
-0.812 | 0.56 | N | 0.302 | 0.272 | 0.520427616228 | gnomAD-4.0.0 | 7.96102E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.90803E-04 | 0 | None | 0 | 0 | 0 | 0 | 3.027E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.092 | likely_benign | 0.0775 | benign | -0.374 | Destabilizing | None | N | 0.093 | neutral | N | 0.497202239 | None | None | N |
| S/C | 0.132 | likely_benign | 0.1106 | benign | -0.369 | Destabilizing | None | N | 0.14 | neutral | N | 0.494249661 | None | None | N |
| S/D | 0.485 | ambiguous | 0.4302 | ambiguous | 0.071 | Stabilizing | 0.072 | N | 0.121 | neutral | None | None | None | None | N |
| S/E | 0.4862 | ambiguous | 0.4265 | ambiguous | -0.02 | Destabilizing | 0.031 | N | 0.12 | neutral | None | None | None | None | N |
| S/F | 0.2637 | likely_benign | 0.2308 | benign | -0.943 | Destabilizing | 0.56 | D | 0.302 | neutral | N | 0.47433498 | None | None | N |
| S/G | 0.0986 | likely_benign | 0.082 | benign | -0.486 | Destabilizing | 0.016 | N | 0.158 | neutral | None | None | None | None | N |
| S/H | 0.2827 | likely_benign | 0.2419 | benign | -0.902 | Destabilizing | 0.628 | D | 0.279 | neutral | None | None | None | None | N |
| S/I | 0.1987 | likely_benign | 0.1547 | benign | -0.208 | Destabilizing | 0.072 | N | 0.313 | neutral | None | None | None | None | N |
| S/K | 0.4715 | ambiguous | 0.4202 | ambiguous | -0.549 | Destabilizing | 0.031 | N | 0.116 | neutral | None | None | None | None | N |
| S/L | 0.1047 | likely_benign | 0.0869 | benign | -0.208 | Destabilizing | 0.031 | N | 0.261 | neutral | None | None | None | None | N |
| S/M | 0.2193 | likely_benign | 0.1668 | benign | -0.077 | Destabilizing | 0.628 | D | 0.271 | neutral | None | None | None | None | N |
| S/N | 0.1434 | likely_benign | 0.1074 | benign | -0.289 | Destabilizing | 0.136 | N | 0.145 | neutral | None | None | None | None | N |
| S/P | 0.0804 | likely_benign | 0.0768 | benign | -0.234 | Destabilizing | None | N | 0.084 | neutral | N | 0.437057858 | None | None | N |
| S/Q | 0.349 | ambiguous | 0.2801 | benign | -0.525 | Destabilizing | 0.136 | N | 0.254 | neutral | None | None | None | None | N |
| S/R | 0.4485 | ambiguous | 0.413 | ambiguous | -0.292 | Destabilizing | 0.136 | N | 0.337 | neutral | None | None | None | None | N |
| S/T | 0.097 | likely_benign | 0.0771 | benign | -0.382 | Destabilizing | None | N | 0.109 | neutral | N | 0.440287377 | None | None | N |
| S/V | 0.2007 | likely_benign | 0.1566 | benign | -0.234 | Destabilizing | 0.016 | N | 0.234 | neutral | None | None | None | None | N |
| S/W | 0.3772 | ambiguous | 0.3867 | ambiguous | -0.961 | Destabilizing | 0.864 | D | 0.263 | neutral | None | None | None | None | N |
| S/Y | 0.2265 | likely_benign | 0.2198 | benign | -0.682 | Destabilizing | 0.56 | D | 0.281 | neutral | N | 0.493996171 | 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.