Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35959 | 108100;108101;108102 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| N2AB | 34318 | 103177;103178;103179 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| N2A | 33391 | 100396;100397;100398 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| N2B | 26894 | 80905;80906;80907 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| Novex-1 | 27019 | 81280;81281;81282 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| Novex-2 | 27086 | 81481;81482;81483 | chr2:178527113;178527112;178527111 | chr2:179391840;179391839;179391838 |
| 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/T | rs1686725786  |
None | None | N | 0.131 | 0.355 | 0.572071643794 | gnomAD-4.0.0 | 1.5909E-06 | None | None | None | 0.217(OBSL1) -0.344(OBSCN) | N | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs1220326083 |
None | 0.019 | N | 0.193 | 0.213 | 0.464870050199 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | -0.147(OBSL1) -0.821(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| M/V | rs1220326083 |
None | 0.019 | N | 0.193 | 0.213 | 0.464870050199 | gnomAD-4.0.0 | 3.42075E-06 | None | None | None | -0.147(OBSL1) -0.821(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49704E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4948 | ambiguous | 0.4664 | ambiguous | -1.237 | Destabilizing | 0.025 | N | 0.222 | neutral | None | None | None | -0.171(OBSL1) -0.802(OBSCN) | N |
| M/C | 0.8582 | likely_pathogenic | 0.8354 | pathogenic | -0.985 | Destabilizing | 0.667 | D | 0.382 | neutral | None | None | None | 0.425(OBSL1) 0.093(OBSCN) | N |
| M/D | 0.8685 | likely_pathogenic | 0.8715 | pathogenic | -0.127 | Destabilizing | 0.22 | N | 0.424 | neutral | None | None | None | -0.858(OBSL1) -0.506(OBSCN) | N |
| M/E | 0.5417 | ambiguous | 0.5075 | ambiguous | -0.126 | Destabilizing | 0.104 | N | 0.4 | neutral | None | None | None | -0.895(OBSL1) -0.561(OBSCN) | N |
| M/F | 0.574 | likely_pathogenic | 0.5782 | pathogenic | -0.4 | Destabilizing | 0.364 | N | 0.288 | neutral | None | None | None | 0.159(OBSL1) -0.393(OBSCN) | N |
| M/G | 0.6954 | likely_pathogenic | 0.6882 | pathogenic | -1.516 | Destabilizing | 0.104 | N | 0.419 | neutral | None | None | None | -0.197(OBSL1) -0.796(OBSCN) | N |
| M/H | 0.6425 | likely_pathogenic | 0.5996 | pathogenic | -0.588 | Destabilizing | 0.859 | D | 0.393 | neutral | None | None | None | 0.136(OBSL1) -0.135(OBSCN) | N |
| M/I | 0.6013 | likely_pathogenic | 0.6 | pathogenic | -0.547 | Destabilizing | 0.042 | N | 0.22 | neutral | N | 0.452846535 | None | -0.15(OBSL1) -0.834(OBSCN) | N |
| M/K | 0.2227 | likely_benign | 0.1829 | benign | -0.202 | Destabilizing | 0.081 | N | 0.336 | neutral | N | 0.408572895 | None | -0.014(OBSL1) -0.452(OBSCN) | N |
| M/L | 0.1721 | likely_benign | 0.1816 | benign | -0.547 | Destabilizing | 0.008 | N | 0.22 | neutral | N | 0.432316547 | None | -0.15(OBSL1) -0.834(OBSCN) | N |
| M/N | 0.6394 | likely_pathogenic | 0.618 | pathogenic | -0.05 | Destabilizing | 0.22 | N | 0.407 | neutral | None | None | None | -0.029(OBSL1) -0.585(OBSCN) | N |
| M/P | 0.8429 | likely_pathogenic | 0.8563 | pathogenic | -0.748 | Destabilizing | 0.364 | N | 0.415 | neutral | None | None | None | -0.147(OBSL1) -0.821(OBSCN) | N |
| M/Q | 0.3232 | likely_benign | 0.2829 | benign | -0.16 | Destabilizing | 0.364 | N | 0.235 | neutral | None | None | None | -0.023(OBSL1) -0.458(OBSCN) | N |
| M/R | 0.2302 | likely_benign | 0.2004 | benign | 0.288 | Stabilizing | 0.175 | N | 0.345 | neutral | N | 0.381349009 | None | -0.076(OBSL1) -0.463(OBSCN) | N |
| M/S | 0.5255 | ambiguous | 0.4928 | ambiguous | -0.636 | Destabilizing | 0.005 | N | 0.147 | neutral | None | None | None | 0.227(OBSL1) -0.307(OBSCN) | N |
| M/T | 0.1661 | likely_benign | 0.15 | benign | -0.523 | Destabilizing | None | N | 0.131 | neutral | N | 0.391835361 | None | 0.217(OBSL1) -0.344(OBSCN) | N |
| M/V | 0.1703 | likely_benign | 0.1655 | benign | -0.748 | Destabilizing | 0.019 | N | 0.193 | neutral | N | 0.437319722 | None | -0.147(OBSL1) -0.821(OBSCN) | N |
| M/W | 0.752 | likely_pathogenic | 0.7379 | pathogenic | -0.338 | Destabilizing | 0.958 | D | 0.363 | neutral | None | None | None | -0.139(OBSL1) -0.527(OBSCN) | N |
| M/Y | 0.7715 | likely_pathogenic | 0.742 | pathogenic | -0.31 | Destabilizing | 0.667 | D | 0.433 | neutral | None | None | None | 0.165(OBSL1) -0.497(OBSCN) | 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.