Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 7505 | 22738;22739;22740 | chr2:178722274;178722273;178722272 | chr2:179587001;179587000;179586999 |
| N2AB | 7188 | 21787;21788;21789 | chr2:178722274;178722273;178722272 | chr2:179587001;179587000;179586999 |
| N2A | 6261 | 19006;19007;19008 | chr2:178722274;178722273;178722272 | chr2:179587001;179587000;179586999 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs372826489  |
-0.979 | 0.425 | N | 0.461 | 0.351 | None | gnomAD-2.1.1 | 8.65E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.57015E-04 |
| R/G | rs372826489 |
-0.979 | 0.425 | N | 0.461 | 0.351 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs372826489 |
-0.979 | 0.425 | N | 0.461 | 0.351 | None | gnomAD-4.0.0 | 6.27575E-06 | None | None | None | None | N | None | 1.34608E-05 | 3.44566E-05 | None | 0 | 0 | None | 0 | 0 | 4.27275E-06 | 0 | 3.24633E-05 |
| R/K | None | None | 0.002 | N | 0.182 | 0.124 | 0.20549828249 | gnomAD-4.0.0 | 1.38868E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.81537E-06 | 0 | 0 |
| R/S | rs1444059423 |
-0.736 | 0.065 | N | 0.239 | 0.228 | 0.136095386433 | gnomAD-2.1.1 | 4.35E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.94E-05 | None | 0 | 0 | 0 |
| R/S | rs1444059423 |
-0.736 | 0.065 | N | 0.239 | 0.228 | 0.136095386433 | gnomAD-4.0.0 | 1.64859E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.54412E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3289 | likely_benign | 0.3489 | ambiguous | -0.893 | Destabilizing | 0.329 | N | 0.395 | neutral | None | None | None | None | N |
| R/C | 0.2378 | likely_benign | 0.2076 | benign | -0.852 | Destabilizing | 0.995 | D | 0.523 | neutral | None | None | None | None | N |
| R/D | 0.6472 | likely_pathogenic | 0.655 | pathogenic | -0.156 | Destabilizing | 0.329 | N | 0.473 | neutral | None | None | None | None | N |
| R/E | 0.3521 | ambiguous | 0.3561 | ambiguous | -0.074 | Destabilizing | 0.013 | N | 0.199 | neutral | None | None | None | None | N |
| R/F | 0.3578 | ambiguous | 0.3639 | ambiguous | -0.994 | Destabilizing | 0.981 | D | 0.524 | neutral | None | None | None | None | N |
| R/G | 0.2654 | likely_benign | 0.2836 | benign | -1.143 | Destabilizing | 0.425 | N | 0.461 | neutral | N | 0.501265824 | None | None | N |
| R/H | 0.0898 | likely_benign | 0.0897 | benign | -1.356 | Destabilizing | 0.944 | D | 0.565 | neutral | None | None | None | None | N |
| R/I | 0.1665 | likely_benign | 0.1641 | benign | -0.237 | Destabilizing | 0.927 | D | 0.534 | neutral | N | 0.460812657 | None | None | N |
| R/K | 0.0826 | likely_benign | 0.0846 | benign | -0.882 | Destabilizing | 0.002 | N | 0.182 | neutral | N | 0.40853561 | None | None | N |
| R/L | 0.1672 | likely_benign | 0.1716 | benign | -0.237 | Destabilizing | 0.704 | D | 0.515 | neutral | None | None | None | None | N |
| R/M | 0.1982 | likely_benign | 0.2035 | benign | -0.377 | Destabilizing | 0.981 | D | 0.547 | neutral | None | None | None | None | N |
| R/N | 0.4588 | ambiguous | 0.4591 | ambiguous | -0.254 | Destabilizing | 0.031 | N | 0.199 | neutral | None | None | None | None | N |
| R/P | 0.6817 | likely_pathogenic | 0.7167 | pathogenic | -0.436 | Destabilizing | 0.828 | D | 0.557 | neutral | None | None | None | None | N |
| R/Q | 0.0993 | likely_benign | 0.1005 | benign | -0.567 | Destabilizing | 0.704 | D | 0.491 | neutral | None | None | None | None | N |
| R/S | 0.3642 | ambiguous | 0.3896 | ambiguous | -1.062 | Destabilizing | 0.065 | N | 0.239 | neutral | N | 0.428582808 | None | None | N |
| R/T | 0.1705 | likely_benign | 0.1799 | benign | -0.824 | Destabilizing | 0.27 | N | 0.471 | neutral | N | 0.418867247 | None | None | N |
| R/V | 0.2253 | likely_benign | 0.2284 | benign | -0.436 | Destabilizing | 0.828 | D | 0.547 | neutral | None | None | None | None | N |
| R/W | 0.1327 | likely_benign | 0.1397 | benign | -0.672 | Destabilizing | 0.995 | D | 0.545 | neutral | None | None | None | None | N |
| R/Y | 0.2906 | likely_benign | 0.2868 | benign | -0.353 | Destabilizing | 0.981 | D | 0.518 | 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.