Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35790 | 107593;107594;107595 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| N2AB | 34149 | 102670;102671;102672 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| N2A | 33222 | 99889;99890;99891 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| N2B | 26725 | 80398;80399;80400 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| Novex-1 | 26850 | 80773;80774;80775 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| Novex-2 | 26917 | 80974;80975;80976 | chr2:178528283;178528282;178528281 | chr2:179393010;179393009;179393008 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs1687416004  |
None | None | N | 0.135 | 0.119 | 0.367612772649 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/L | rs1687416004 |
None | None | N | 0.135 | 0.119 | 0.367612772649 | gnomAD-4.0.0 | 6.5716E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs1188337689 |
1.085 | None | N | 0.173 | 0.11 | 0.192905019026 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/R | rs1188337689 |
1.085 | None | N | 0.173 | 0.11 | 0.192905019026 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs1188337689 |
1.085 | None | N | 0.173 | 0.11 | 0.192905019026 | gnomAD-4.0.0 | 2.56222E-06 | None | None | None | None | N | None | 3.38203E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1618 | likely_benign | 0.1666 | benign | -0.882 | Destabilizing | None | N | 0.153 | neutral | None | None | None | None | N |
| M/C | 0.6648 | likely_pathogenic | 0.7081 | pathogenic | -0.868 | Destabilizing | 0.003 | N | 0.295 | neutral | None | None | None | None | N |
| M/D | 0.5963 | likely_pathogenic | 0.6091 | pathogenic | 0.398 | Stabilizing | None | N | 0.181 | neutral | None | None | None | None | N |
| M/E | 0.343 | ambiguous | 0.3142 | benign | 0.401 | Stabilizing | None | N | 0.155 | neutral | None | None | None | None | N |
| M/F | 0.3244 | likely_benign | 0.3227 | benign | -0.108 | Destabilizing | None | N | 0.163 | neutral | None | None | None | None | N |
| M/G | 0.4903 | ambiguous | 0.4951 | ambiguous | -1.151 | Destabilizing | None | N | 0.193 | neutral | None | None | None | None | N |
| M/H | 0.3157 | likely_benign | 0.3205 | benign | -0.197 | Destabilizing | None | N | 0.147 | neutral | None | None | None | None | N |
| M/I | 0.2091 | likely_benign | 0.2096 | benign | -0.235 | Destabilizing | None | N | 0.163 | neutral | N | 0.374673752 | None | None | N |
| M/K | 0.1628 | likely_benign | 0.1292 | benign | 0.181 | Stabilizing | None | N | 0.168 | neutral | N | 0.415786869 | None | None | N |
| M/L | 0.1228 | likely_benign | 0.117 | benign | -0.235 | Destabilizing | None | N | 0.135 | neutral | N | 0.400166843 | None | None | N |
| M/N | 0.1829 | likely_benign | 0.2105 | benign | 0.251 | Stabilizing | None | N | 0.145 | neutral | None | None | None | None | N |
| M/P | 0.8649 | likely_pathogenic | 0.8922 | pathogenic | -0.42 | Destabilizing | None | N | 0.171 | neutral | None | None | None | None | N |
| M/Q | 0.1767 | likely_benign | 0.1713 | benign | 0.179 | Stabilizing | None | N | 0.16 | neutral | None | None | None | None | N |
| M/R | 0.1489 | likely_benign | 0.121 | benign | 0.599 | Stabilizing | None | N | 0.173 | neutral | N | 0.396222461 | None | None | N |
| M/S | 0.1608 | likely_benign | 0.1773 | benign | -0.361 | Destabilizing | None | N | 0.152 | neutral | None | None | None | None | N |
| M/T | 0.0496 | likely_benign | 0.0552 | benign | -0.237 | Destabilizing | None | N | 0.152 | neutral | N | 0.302656152 | None | None | N |
| M/V | 0.0942 | likely_benign | 0.0889 | benign | -0.42 | Destabilizing | None | N | 0.147 | neutral | N | 0.382754518 | None | None | N |
| M/W | 0.6184 | likely_pathogenic | 0.5918 | pathogenic | -0.07 | Destabilizing | 0.023 | N | 0.332 | neutral | None | None | None | None | N |
| M/Y | 0.5083 | ambiguous | 0.5069 | ambiguous | 0.015 | Stabilizing | None | N | 0.175 | 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.