Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35983 | 108172;108173;108174 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| N2AB | 34342 | 103249;103250;103251 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| N2A | 33415 | 100468;100469;100470 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| N2B | 26918 | 80977;80978;80979 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| Novex-1 | 27043 | 81352;81353;81354 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| Novex-2 | 27110 | 81553;81554;81555 | chr2:178527041;178527040;178527039 | chr2:179391768;179391767;179391766 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs764418855  |
-0.987 | 0.454 | D | 0.46 | 0.222 | 0.197625483188 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | -0.8(OBSL1) -0.08(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| T/A | rs764418855 |
-0.987 | 0.454 | D | 0.46 | 0.222 | 0.197625483188 | gnomAD-4.0.0 | 6.84266E-07 | None | None | None | -0.8(OBSL1) -0.08(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16001E-05 | 0 |
| T/P | rs764418855 |
-0.702 | 0.966 | N | 0.625 | 0.492 | 0.479744053436 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | -0.992(OBSL1) -0.091(OBSCN) | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 1.66389E-04 |
| T/P | rs764418855 |
-0.702 | 0.966 | N | 0.625 | 0.492 | 0.479744053436 | gnomAD-4.0.0 | 4.78986E-06 | None | None | None | -0.992(OBSL1) -0.091(OBSCN) | N | None | 0 | 2.23654E-05 | None | 0 | 0 | None | 0 | 0 | 5.39696E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1278 | likely_benign | 0.1206 | benign | -0.372 | Destabilizing | 0.454 | N | 0.46 | neutral | D | 0.525093422 | None | -0.8(OBSL1) -0.08(OBSCN) | N |
| T/C | 0.762 | likely_pathogenic | 0.7546 | pathogenic | -0.292 | Destabilizing | 0.998 | D | 0.569 | neutral | None | None | None | -1.329(OBSL1) -0.134(OBSCN) | N |
| T/D | 0.6726 | likely_pathogenic | 0.6478 | pathogenic | 0.31 | Stabilizing | 0.016 | N | 0.328 | neutral | None | None | None | -0.569(OBSL1) -0.252(OBSCN) | N |
| T/E | 0.4861 | ambiguous | 0.4556 | ambiguous | 0.253 | Stabilizing | 0.728 | D | 0.521 | neutral | None | None | None | -0.718(OBSL1) -0.319(OBSCN) | N |
| T/F | 0.5928 | likely_pathogenic | 0.5689 | pathogenic | -0.792 | Destabilizing | 0.974 | D | 0.659 | neutral | None | None | None | -0.922(OBSL1) 0.019(OBSCN) | N |
| T/G | 0.5674 | likely_pathogenic | 0.5468 | ambiguous | -0.529 | Destabilizing | 0.728 | D | 0.589 | neutral | None | None | None | -0.718(OBSL1) -0.083(OBSCN) | N |
| T/H | 0.5418 | ambiguous | 0.5114 | ambiguous | -0.786 | Destabilizing | 0.081 | N | 0.526 | neutral | None | None | None | -0.41(OBSL1) 0.541(OBSCN) | N |
| T/I | 0.4156 | ambiguous | 0.3867 | ambiguous | -0.073 | Destabilizing | 0.966 | D | 0.625 | neutral | N | 0.507547811 | None | -1.101(OBSL1) -0.104(OBSCN) | N |
| T/K | 0.339 | likely_benign | 0.3041 | benign | -0.329 | Destabilizing | 0.842 | D | 0.557 | neutral | None | None | None | -2.046(OBSL1) -0.405(OBSCN) | N |
| T/L | 0.2996 | likely_benign | 0.2679 | benign | -0.073 | Destabilizing | 0.842 | D | 0.559 | neutral | None | None | None | -1.101(OBSL1) -0.104(OBSCN) | N |
| T/M | 0.1668 | likely_benign | 0.1544 | benign | 0.008 | Stabilizing | 0.998 | D | 0.564 | neutral | None | None | None | -0.871(OBSL1) 0.327(OBSCN) | N |
| T/N | 0.2917 | likely_benign | 0.2825 | benign | -0.157 | Destabilizing | 0.051 | N | 0.295 | neutral | N | 0.48494031 | None | -1.318(OBSL1) -0.637(OBSCN) | N |
| T/P | 0.4435 | ambiguous | 0.3841 | ambiguous | -0.142 | Destabilizing | 0.966 | D | 0.625 | neutral | N | 0.499356948 | None | -0.992(OBSL1) -0.091(OBSCN) | N |
| T/Q | 0.372 | ambiguous | 0.3499 | ambiguous | -0.337 | Destabilizing | 0.974 | D | 0.631 | neutral | None | None | None | -1.363(OBSL1) -0.487(OBSCN) | N |
| T/R | 0.2729 | likely_benign | 0.242 | benign | -0.091 | Destabilizing | 0.949 | D | 0.624 | neutral | None | None | None | -2.039(OBSL1) -0.326(OBSCN) | N |
| T/S | 0.1846 | likely_benign | 0.1853 | benign | -0.399 | Destabilizing | 0.022 | N | 0.171 | neutral | N | 0.476838115 | None | -1.461(OBSL1) -0.503(OBSCN) | N |
| T/V | 0.267 | likely_benign | 0.2576 | benign | -0.142 | Destabilizing | 0.842 | D | 0.512 | neutral | None | None | None | -0.992(OBSL1) -0.091(OBSCN) | N |
| T/W | 0.8859 | likely_pathogenic | 0.8743 | pathogenic | -0.797 | Destabilizing | 0.998 | D | 0.676 | prob.neutral | None | None | None | -0.948(OBSL1) 0.078(OBSCN) | N |
| T/Y | 0.6521 | likely_pathogenic | 0.6283 | pathogenic | -0.507 | Destabilizing | 0.949 | D | 0.663 | neutral | None | None | None | -0.772(OBSL1) 0.204(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.