Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 13894 | 41905;41906;41907 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| N2AB | 12253 | 36982;36983;36984 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| N2A | 11326 | 34201;34202;34203 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| N2B | 4829 | 14710;14711;14712 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| Novex-1 | 4954 | 15085;15086;15087 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| Novex-2 | 5021 | 15286;15287;15288 | chr2:178635644;178635643;178635642 | chr2:179500371;179500370;179500369 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs1409834949  |
-0.225 | 0.006 | N | 0.362 | 0.056 | 0.333651784274 | gnomAD-2.1.1 | 4.46E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1E-05 | 0 |
| A/V | rs1409834949 |
-0.225 | 0.006 | N | 0.362 | 0.056 | 0.333651784274 | gnomAD-4.0.0 | 1.63189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.92665E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3691 | ambiguous | 0.381 | ambiguous | -0.393 | Destabilizing | 0.204 | N | 0.564 | neutral | None | None | None | None | N |
| A/D | 0.4667 | ambiguous | 0.546 | ambiguous | -1.061 | Destabilizing | 0.006 | N | 0.555 | neutral | N | 0.36340433 | None | None | N |
| A/E | 0.3184 | likely_benign | 0.3608 | ambiguous | -0.985 | Destabilizing | None | N | 0.435 | neutral | None | None | None | None | N |
| A/F | 0.2881 | likely_benign | 0.3124 | benign | -0.63 | Destabilizing | 0.204 | N | 0.701 | prob.delet. | None | None | None | None | N |
| A/G | 0.187 | likely_benign | 0.2203 | benign | -1.089 | Destabilizing | 0.002 | N | 0.43 | neutral | N | 0.417163264 | None | None | N |
| A/H | 0.3987 | ambiguous | 0.4242 | ambiguous | -1.416 | Destabilizing | 0.204 | N | 0.618 | neutral | None | None | None | None | N |
| A/I | 0.2164 | likely_benign | 0.237 | benign | 0.163 | Stabilizing | 0.018 | N | 0.625 | neutral | None | None | None | None | N |
| A/K | 0.443 | ambiguous | 0.4859 | ambiguous | -0.85 | Destabilizing | None | N | 0.397 | neutral | None | None | None | None | N |
| A/L | 0.1819 | likely_benign | 0.1997 | benign | 0.163 | Stabilizing | 0.007 | N | 0.53 | neutral | None | None | None | None | N |
| A/M | 0.217 | likely_benign | 0.2405 | benign | 0.18 | Stabilizing | 0.204 | N | 0.561 | neutral | None | None | None | None | N |
| A/N | 0.264 | likely_benign | 0.3022 | benign | -0.699 | Destabilizing | 0.007 | N | 0.547 | neutral | None | None | None | None | N |
| A/P | 0.6796 | likely_pathogenic | 0.7424 | pathogenic | -0.089 | Destabilizing | 0.052 | N | 0.602 | neutral | N | 0.415707821 | None | None | N |
| A/Q | 0.3192 | likely_benign | 0.3342 | benign | -0.684 | Destabilizing | 0.035 | N | 0.605 | neutral | None | None | None | None | N |
| A/R | 0.3755 | ambiguous | 0.3904 | ambiguous | -0.782 | Destabilizing | 0.007 | N | 0.529 | neutral | None | None | None | None | N |
| A/S | 0.0821 | likely_benign | 0.0884 | benign | -1.109 | Destabilizing | None | N | 0.198 | neutral | N | 0.362250748 | None | None | N |
| A/T | 0.0693 | likely_benign | 0.0733 | benign | -0.92 | Destabilizing | None | N | 0.229 | neutral | N | 0.308728163 | None | None | N |
| A/V | 0.1326 | likely_benign | 0.1415 | benign | -0.089 | Destabilizing | 0.006 | N | 0.362 | neutral | N | 0.414562129 | None | None | N |
| A/W | 0.7024 | likely_pathogenic | 0.7274 | pathogenic | -1.203 | Destabilizing | 0.747 | D | 0.683 | prob.neutral | None | None | None | None | N |
| A/Y | 0.3901 | ambiguous | 0.4128 | ambiguous | -0.659 | Destabilizing | 0.204 | N | 0.698 | prob.delet. | 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.