Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4714 | 14365;14366;14367 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| N2AB | 4397 | 13414;13415;13416 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| N2A | 3470 | 10633;10634;10635 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| N2B | 4351 | 13276;13277;13278 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| Novex-1 | 4476 | 13651;13652;13653 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| Novex-2 | 4543 | 13852;13853;13854 | chr2:178738313;178738312;178738311 | chr2:179603040;179603039;179603038 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/D | rs750125429  |
-0.914 | 0.997 | D | 0.791 | 0.814 | 0.736588646186 | gnomAD-2.1.1 | 8.23E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.08348E-03 | None | 0 | None | 0 | 1.56E-05 | 0 |
| G/D | rs750125429 |
-0.914 | 0.997 | D | 0.791 | 0.814 | 0.736588646186 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 9.61908E-04 | None | 0 | 0 | 0 | 0 | 0 |
| G/D | rs750125429 |
-0.914 | 0.997 | D | 0.791 | 0.814 | 0.736588646186 |
Liu (2008)
| None |
DCM 
|
het | None | None | I | Genetic analysis of CN DCM families (n = 2, 2 affected) | None | None | None | None | None | None | None | None | None | None | None |
| G/D | rs750125429 |
-0.914 | 0.997 | D | 0.791 | 0.814 | 0.736588646186 | gnomAD-4.0.0 | 2.35542E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.92242E-04 | None | 0 | 0 | 5.0863E-06 | 0 | 1.6021E-05 |
| G/S | rs757944467 |
-0.634 | 0.997 | D | 0.763 | 0.757 | 0.684895203126 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| G/S | rs757944467 |
-0.634 | 0.997 | D | 0.763 | 0.757 | 0.684895203126 | gnomAD-4.0.0 | 3.18439E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.7188E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.654 | likely_pathogenic | 0.6852 | pathogenic | -0.529 | Destabilizing | 0.995 | D | 0.697 | prob.neutral | D | 0.660593598 | None | None | I |
| G/C | 0.8428 | likely_pathogenic | 0.8203 | pathogenic | -0.831 | Destabilizing | 1.0 | D | 0.783 | deleterious | D | 0.801217252 | None | None | I |
| G/D | 0.8677 | likely_pathogenic | 0.8926 | pathogenic | -0.927 | Destabilizing | 0.997 | D | 0.791 | deleterious | D | 0.661979814 | None | None | I |
| G/E | 0.8966 | likely_pathogenic | 0.879 | pathogenic | -1.063 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | I |
| G/F | 0.9605 | likely_pathogenic | 0.9588 | pathogenic | -1.102 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| G/H | 0.9256 | likely_pathogenic | 0.9162 | pathogenic | -0.93 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| G/I | 0.9676 | likely_pathogenic | 0.971 | pathogenic | -0.461 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| G/K | 0.9718 | likely_pathogenic | 0.9608 | pathogenic | -1.137 | Destabilizing | 0.999 | D | 0.772 | deleterious | None | None | None | None | I |
| G/L | 0.929 | likely_pathogenic | 0.9327 | pathogenic | -0.461 | Destabilizing | 0.999 | D | 0.773 | deleterious | None | None | None | None | I |
| G/M | 0.9629 | likely_pathogenic | 0.964 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| G/N | 0.7386 | likely_pathogenic | 0.7306 | pathogenic | -0.711 | Destabilizing | 0.669 | D | 0.57 | neutral | None | None | None | None | I |
| G/P | 0.9925 | likely_pathogenic | 0.9951 | pathogenic | -0.446 | Destabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | I |
| G/Q | 0.8936 | likely_pathogenic | 0.8842 | pathogenic | -0.996 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
| G/R | 0.9244 | likely_pathogenic | 0.9018 | pathogenic | -0.661 | Destabilizing | 0.999 | D | 0.784 | deleterious | D | 0.731092808 | None | None | I |
| G/S | 0.4374 | ambiguous | 0.4418 | ambiguous | -0.884 | Destabilizing | 0.997 | D | 0.763 | deleterious | D | 0.639876784 | None | None | I |
| G/T | 0.8259 | likely_pathogenic | 0.8394 | pathogenic | -0.953 | Destabilizing | 0.999 | D | 0.771 | deleterious | None | None | None | None | I |
| G/V | 0.9316 | likely_pathogenic | 0.9408 | pathogenic | -0.446 | Destabilizing | 0.999 | D | 0.772 | deleterious | D | 0.687570159 | None | None | I |
| G/W | 0.9246 | likely_pathogenic | 0.9101 | pathogenic | -1.323 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | I |
| G/Y | 0.932 | likely_pathogenic | 0.9212 | pathogenic | -0.97 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | I |
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.