Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25562 | 76909;76910;76911 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| N2AB | 23921 | 71986;71987;71988 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| N2A | 22994 | 69205;69206;69207 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| N2B | 16497 | 49714;49715;49716 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| Novex-1 | 16622 | 50089;50090;50091 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| Novex-2 | 16689 | 50290;50291;50292 | chr2:178569448;178569447;178569446 | chr2:179434175;179434174;179434173 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | rs1400963847  |
-0.718 | 0.822 | N | 0.405 | 0.295 | 0.275641507738 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14758E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs1400963847 |
-0.718 | 0.822 | N | 0.405 | 0.295 | 0.275641507738 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs1400963847 |
-0.718 | 0.822 | N | 0.405 | 0.295 | 0.275641507738 | gnomAD-4.0.0 | 6.57454E-06 | None | None | None | None | N | None | 2.41255E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1441 | likely_benign | 0.1516 | benign | -0.545 | Destabilizing | 0.717 | D | 0.417 | neutral | None | None | None | None | N |
| S/C | 0.2029 | likely_benign | 0.2041 | benign | -0.36 | Destabilizing | 0.997 | D | 0.555 | neutral | N | 0.516220208 | None | None | N |
| S/D | 0.7558 | likely_pathogenic | 0.7876 | pathogenic | 0.703 | Stabilizing | 0.754 | D | 0.419 | neutral | None | None | None | None | N |
| S/E | 0.8601 | likely_pathogenic | 0.8783 | pathogenic | 0.664 | Stabilizing | 0.86 | D | 0.383 | neutral | None | None | None | None | N |
| S/F | 0.4864 | ambiguous | 0.5193 | ambiguous | -0.992 | Destabilizing | 0.993 | D | 0.571 | neutral | None | None | None | None | N |
| S/G | 0.1965 | likely_benign | 0.1922 | benign | -0.714 | Destabilizing | 0.822 | D | 0.405 | neutral | N | 0.503699429 | None | None | N |
| S/H | 0.6291 | likely_pathogenic | 0.647 | pathogenic | -1.038 | Destabilizing | 0.978 | D | 0.528 | neutral | None | None | None | None | N |
| S/I | 0.4684 | ambiguous | 0.4943 | ambiguous | -0.218 | Destabilizing | 0.97 | D | 0.565 | neutral | N | 0.487569342 | None | None | N |
| S/K | 0.931 | likely_pathogenic | 0.9389 | pathogenic | -0.241 | Destabilizing | 0.754 | D | 0.396 | neutral | None | None | None | None | N |
| S/L | 0.2165 | likely_benign | 0.2294 | benign | -0.218 | Destabilizing | 0.86 | D | 0.466 | neutral | None | None | None | None | N |
| S/M | 0.3709 | ambiguous | 0.385 | ambiguous | -0.197 | Destabilizing | 0.998 | D | 0.533 | neutral | None | None | None | None | N |
| S/N | 0.3657 | ambiguous | 0.3521 | ambiguous | -0.141 | Destabilizing | 0.058 | N | 0.257 | neutral | N | 0.498541539 | None | None | N |
| S/P | 0.8639 | likely_pathogenic | 0.8794 | pathogenic | -0.296 | Destabilizing | 0.993 | D | 0.49 | neutral | None | None | None | None | N |
| S/Q | 0.7754 | likely_pathogenic | 0.7879 | pathogenic | -0.244 | Destabilizing | 0.956 | D | 0.436 | neutral | None | None | None | None | N |
| S/R | 0.8876 | likely_pathogenic | 0.8963 | pathogenic | -0.15 | Destabilizing | 0.032 | N | 0.251 | neutral | N | 0.487440757 | None | None | N |
| S/T | 0.1131 | likely_benign | 0.1206 | benign | -0.268 | Destabilizing | 0.822 | D | 0.409 | neutral | N | 0.490210057 | None | None | N |
| S/V | 0.3947 | ambiguous | 0.4183 | ambiguous | -0.296 | Destabilizing | 0.978 | D | 0.519 | neutral | None | None | None | None | N |
| S/W | 0.6933 | likely_pathogenic | 0.7203 | pathogenic | -0.988 | Destabilizing | 0.998 | D | 0.65 | neutral | None | None | None | None | N |
| S/Y | 0.3915 | ambiguous | 0.4099 | ambiguous | -0.688 | Destabilizing | 0.993 | D | 0.571 | 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.