Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35915 | 107968;107969;107970 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| N2AB | 34274 | 103045;103046;103047 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| N2A | 33347 | 100264;100265;100266 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| N2B | 26850 | 80773;80774;80775 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| Novex-1 | 26975 | 81148;81149;81150 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| Novex-2 | 27042 | 81349;81350;81351 | chr2:178527245;178527244;178527243 | chr2:179391972;179391971;179391970 |
| 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/K | rs768221453  |
None | 0.998 | N | 0.692 | 0.434 | 0.436993770938 | gnomAD-4.0.0 | 3.18428E-06 | None | None | None | -2.693(OBSL1) -1.352(OBSCN) | N | None | 1.13071E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/P | None | -0.588 | 0.999 | N | 0.751 | 0.467 | 0.48286525802 |
Evila (2016)
| None |
TMD 
|
comp het with E28338fs | None | -1.476(OBSL1) -0.66(OBSCN) | N | Genetic analysis of genes in 10 TMD families; co-segregation in 2-generation family (recessive inheritance, n = 3, 3 affected (total 4)); variant prioritisation; comp het with E28338fs | None | None | None | None | None | None | None | None | None | None | None |
| T/P | None | -0.588 | 0.999 | N | 0.751 | 0.467 | 0.48286525802 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | -1.476(OBSL1) -0.66(OBSCN) | N | None | 6.33473E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.3419 | ambiguous | 0.4011 | ambiguous | -0.353 | Destabilizing | 0.962 | D | 0.523 | neutral | N | 0.514739489 | None | -1.36(OBSL1) -0.732(OBSCN) | N |
| T/C | 0.869 | likely_pathogenic | 0.8913 | pathogenic | -0.404 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | -1.282(OBSL1) -0.618(OBSCN) | N |
| T/D | 0.9401 | likely_pathogenic | 0.9574 | pathogenic | 0.26 | Stabilizing | 0.998 | D | 0.696 | prob.neutral | None | None | None | -1.612(OBSL1) -1.529(OBSCN) | N |
| T/E | 0.8414 | likely_pathogenic | 0.8905 | pathogenic | 0.238 | Stabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | -1.683(OBSL1) -1.512(OBSCN) | N |
| T/F | 0.859 | likely_pathogenic | 0.8931 | pathogenic | -0.637 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | -1.186(OBSL1) -0.334(OBSCN) | N |
| T/G | 0.8194 | likely_pathogenic | 0.8648 | pathogenic | -0.554 | Destabilizing | 0.994 | D | 0.622 | neutral | None | None | None | -1.32(OBSL1) -0.787(OBSCN) | N |
| T/H | 0.7273 | likely_pathogenic | 0.7894 | pathogenic | -0.763 | Destabilizing | 1.0 | D | 0.764 | deleterious | None | None | None | -1.212(OBSL1) -0.732(OBSCN) | N |
| T/I | 0.7001 | likely_pathogenic | 0.752 | pathogenic | 0.068 | Stabilizing | 0.999 | D | 0.752 | deleterious | N | 0.509832315 | None | -1.551(OBSL1) -0.645(OBSCN) | N |
| T/K | 0.7269 | likely_pathogenic | 0.7756 | pathogenic | -0.38 | Destabilizing | 0.998 | D | 0.692 | prob.neutral | N | 0.489091683 | None | -2.693(OBSL1) -1.352(OBSCN) | N |
| T/L | 0.4558 | ambiguous | 0.5044 | ambiguous | 0.068 | Stabilizing | 0.997 | D | 0.597 | neutral | None | None | None | -1.551(OBSL1) -0.645(OBSCN) | N |
| T/M | 0.2723 | likely_benign | 0.3234 | benign | -0.036 | Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | -1.036(OBSL1) -0.508(OBSCN) | N |
| T/N | 0.6535 | likely_pathogenic | 0.7294 | pathogenic | -0.366 | Destabilizing | 0.998 | D | 0.641 | neutral | None | None | None | -1.031(OBSL1) -0.23(OBSCN) | N |
| T/P | 0.794 | likely_pathogenic | 0.8238 | pathogenic | -0.041 | Destabilizing | 0.999 | D | 0.751 | deleterious | N | 0.495222441 | None | -1.476(OBSL1) -0.66(OBSCN) | N |
| T/Q | 0.6765 | likely_pathogenic | 0.7501 | pathogenic | -0.463 | Destabilizing | 0.999 | D | 0.753 | deleterious | None | None | None | -1.308(OBSL1) -0.428(OBSCN) | N |
| T/R | 0.6298 | likely_pathogenic | 0.6926 | pathogenic | -0.176 | Destabilizing | 0.999 | D | 0.741 | deleterious | N | 0.475450383 | None | -2.279(OBSL1) -1.196(OBSCN) | N |
| T/S | 0.47 | ambiguous | 0.5692 | pathogenic | -0.585 | Destabilizing | 0.825 | D | 0.367 | neutral | N | 0.460886362 | None | -1.691(OBSL1) -0.625(OBSCN) | N |
| T/V | 0.5081 | ambiguous | 0.5598 | ambiguous | -0.041 | Destabilizing | 0.997 | D | 0.526 | neutral | None | None | None | -1.476(OBSL1) -0.66(OBSCN) | N |
| T/W | 0.9385 | likely_pathogenic | 0.954 | pathogenic | -0.676 | Destabilizing | 1.0 | D | 0.752 | deleterious | None | None | None | -1.405(OBSL1) -0.692(OBSCN) | N |
| T/Y | 0.8407 | likely_pathogenic | 0.8734 | pathogenic | -0.372 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | -1.017(OBSL1) -0.248(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.