Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14573 | 43942;43943;43944 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| N2AB | 12932 | 39019;39020;39021 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| N2A | 12005 | 36238;36239;36240 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| N2B | 5508 | 16747;16748;16749 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| Novex-1 | 5633 | 17122;17123;17124 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| Novex-2 | 5700 | 17323;17324;17325 | chr2:178632177;178632176;178632175 | chr2:179496904;179496903;179496902 |
| 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 | rs755610701  |
0.388 | None | N | 0.083 | 0.147 | 0.17258766438 | gnomAD-2.1.1 | 4.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.24E-06 | 0 |
| M/L | rs755610701 |
0.388 | None | N | 0.083 | 0.147 | 0.17258766438 | gnomAD-4.0.0 | 2.06059E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70507E-06 | 0 | 0 |
| M/V | rs755610701 |
0.197 | None | N | 0.133 | 0.143 | 0.107399877778 | gnomAD-2.1.1 | 1.47E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.23E-05 | 0 |
| M/V | rs755610701 |
0.197 | None | N | 0.133 | 0.143 | 0.107399877778 | 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 |
| M/V | rs755610701 |
0.197 | None | N | 0.133 | 0.143 | 0.107399877778 | gnomAD-4.0.0 | 1.43037E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.95408E-05 | 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 | 0.3316 | likely_benign | 0.3063 | benign | -0.675 | Destabilizing | 0.002 | N | 0.239 | neutral | None | None | None | None | N |
| M/C | 0.6141 | likely_pathogenic | 0.6103 | pathogenic | -0.657 | Destabilizing | 0.316 | N | 0.332 | neutral | None | None | None | None | N |
| M/D | 0.6379 | likely_pathogenic | 0.5877 | pathogenic | 0.687 | Stabilizing | 0.009 | N | 0.309 | neutral | None | None | None | None | N |
| M/E | 0.3436 | ambiguous | 0.3092 | benign | 0.7 | Stabilizing | 0.002 | N | 0.249 | neutral | None | None | None | None | N |
| M/F | 0.2052 | likely_benign | 0.1857 | benign | 0.065 | Stabilizing | 0.004 | N | 0.194 | neutral | None | None | None | None | N |
| M/G | 0.5458 | ambiguous | 0.5281 | ambiguous | -0.942 | Destabilizing | 0.004 | N | 0.309 | neutral | None | None | None | None | N |
| M/H | 0.3406 | ambiguous | 0.3171 | benign | -0.057 | Destabilizing | 0.316 | N | 0.446 | neutral | None | None | None | None | N |
| M/I | 0.1141 | likely_benign | 0.0965 | benign | -0.035 | Destabilizing | None | N | 0.069 | neutral | N | 0.413888727 | None | None | N |
| M/K | 0.1333 | likely_benign | 0.1202 | benign | 0.365 | Stabilizing | None | N | 0.123 | neutral | N | 0.371062647 | None | None | N |
| M/L | 0.0694 | likely_benign | 0.0699 | benign | -0.035 | Destabilizing | None | N | 0.083 | neutral | N | 0.382516984 | None | None | N |
| M/N | 0.3308 | likely_benign | 0.2924 | benign | 0.4 | Stabilizing | 0.009 | N | 0.29 | neutral | None | None | None | None | N |
| M/P | 0.7876 | likely_pathogenic | 0.7808 | pathogenic | -0.218 | Destabilizing | 0.018 | N | 0.35 | neutral | None | None | None | None | N |
| M/Q | 0.2002 | likely_benign | 0.1868 | benign | 0.38 | Stabilizing | 0.009 | N | 0.201 | neutral | None | None | None | None | N |
| M/R | 0.1625 | likely_benign | 0.1572 | benign | 0.688 | Stabilizing | 0.001 | N | 0.253 | neutral | N | 0.486240261 | None | None | N |
| M/S | 0.339 | likely_benign | 0.3193 | benign | -0.204 | Destabilizing | 0.002 | N | 0.247 | neutral | None | None | None | None | N |
| M/T | 0.2181 | likely_benign | 0.2047 | benign | -0.067 | Destabilizing | 0.003 | N | 0.254 | neutral | N | 0.48702858 | None | None | N |
| M/V | 0.0842 | likely_benign | 0.0808 | benign | -0.218 | Destabilizing | None | N | 0.133 | neutral | N | 0.422498498 | None | None | N |
| M/W | 0.459 | ambiguous | 0.4308 | ambiguous | 0.06 | Stabilizing | 0.316 | N | 0.319 | neutral | None | None | None | None | N |
| M/Y | 0.392 | ambiguous | 0.3519 | ambiguous | 0.178 | Stabilizing | 0.018 | N | 0.391 | 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.