Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1159 | 3700;3701;3702 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| N2AB | 1159 | 3700;3701;3702 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| N2A | 1159 | 3700;3701;3702 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| N2B | 1113 | 3562;3563;3564 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| Novex-1 | 1113 | 3562;3563;3564 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| Novex-2 | 1113 | 3562;3563;3564 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
| Novex-3 | 1159 | 3700;3701;3702 | chr2:178781169;178781168;178781167 | chr2:179645896;179645895;179645894 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs797046063  |
-0.447 | 1.0 | N | 0.745 | 0.556 | 0.7175160923 | gnomAD-2.1.1 | 7.97E-06 | None | None | None | None | I | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.81E-06 | 0 |
| R/C | rs797046063 |
-0.447 | 1.0 | N | 0.745 | 0.556 | 0.7175160923 | gnomAD-4.0.0 | 3.42062E-06 | None | None | None | None | I | None | 0 | 2.23624E-05 | None | 3.82702E-05 | 0 | None | 0 | 0 | 2.69799E-06 | 0 | 0 |
| R/H | rs149883066 |
-1.464 | 1.0 | N | 0.637 | 0.39 | 0.380223377699 | gnomAD-2.1.1 | 2.39E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.41E-05 | 1.63345E-04 |
| R/H | rs149883066 |
-1.464 | 1.0 | N | 0.637 | 0.39 | 0.380223377699 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| R/H | rs149883066 |
-1.464 | 1.0 | N | 0.637 | 0.39 | 0.380223377699 | gnomAD-4.0.0 | 2.47856E-05 | None | None | None | None | I | None | 0 | 1.66678E-05 | None | 0 | 4.45871E-05 | None | 0 | 0 | 3.05103E-05 | 1.09791E-05 | 0 |
| R/L | rs149883066 |
0.224 | 0.992 | N | 0.643 | 0.434 | None | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | I | None | 0 | 0 | None | 2.98033E-04 | 0 | None | 0 | None | 0 | 0 | 1.63345E-04 |
| R/L | rs149883066 |
0.224 | 0.992 | N | 0.643 | 0.434 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 2.88351E-04 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/L | rs149883066 |
0.224 | 0.992 | N | 0.643 | 0.434 | None | gnomAD-4.0.0 | 1.05339E-05 | None | None | None | None | I | None | 0 | 0 | None | 4.05433E-04 | 0 | None | 0 | 0 | 3.39003E-06 | 0 | 1.60046E-05 |
| R/S | None | -0.779 | 0.984 | N | 0.608 | 0.548 | 0.383590876969 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30685E-04 | None | 0 | 0 | 0 |
| R/S | None | -0.779 | 0.984 | N | 0.608 | 0.548 | 0.383590876969 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92382E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | None | -0.779 | 0.984 | N | 0.608 | 0.548 | 0.383590876969 | gnomAD-4.0.0 | 6.81604E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 6.68807E-05 | None | 0 | 0 | 0 | 8.78407E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9285 | likely_pathogenic | 0.9007 | pathogenic | -1.03 | Destabilizing | 0.931 | D | 0.574 | neutral | None | None | None | None | I |
| R/C | 0.6319 | likely_pathogenic | 0.5392 | ambiguous | -0.897 | Destabilizing | 1.0 | D | 0.745 | deleterious | N | 0.502298605 | None | None | I |
| R/D | 0.9902 | likely_pathogenic | 0.9864 | pathogenic | -0.391 | Destabilizing | 0.996 | D | 0.643 | neutral | None | None | None | None | I |
| R/E | 0.8889 | likely_pathogenic | 0.851 | pathogenic | -0.188 | Destabilizing | 0.97 | D | 0.521 | neutral | None | None | None | None | I |
| R/F | 0.9633 | likely_pathogenic | 0.9473 | pathogenic | -0.308 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | None | None | None | None | I |
| R/G | 0.8775 | likely_pathogenic | 0.8312 | pathogenic | -1.42 | Destabilizing | 0.992 | D | 0.643 | neutral | N | 0.510725339 | None | None | I |
| R/H | 0.3787 | ambiguous | 0.3383 | benign | -1.597 | Destabilizing | 1.0 | D | 0.637 | neutral | N | 0.510265694 | None | None | I |
| R/I | 0.8724 | likely_pathogenic | 0.8116 | pathogenic | 0.066 | Stabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| R/K | 0.2423 | likely_benign | 0.2071 | benign | -0.888 | Destabilizing | 0.155 | N | 0.17 | neutral | None | None | None | None | I |
| R/L | 0.84 | likely_pathogenic | 0.7896 | pathogenic | 0.066 | Stabilizing | 0.992 | D | 0.643 | neutral | N | 0.500854958 | None | None | I |
| R/M | 0.8826 | likely_pathogenic | 0.8216 | pathogenic | -0.429 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | I |
| R/N | 0.9712 | likely_pathogenic | 0.9601 | pathogenic | -0.734 | Destabilizing | 0.985 | D | 0.593 | neutral | None | None | None | None | I |
| R/P | 0.9977 | likely_pathogenic | 0.9969 | pathogenic | -0.281 | Destabilizing | 0.999 | D | 0.69 | prob.neutral | D | 0.568387262 | None | None | I |
| R/Q | 0.295 | likely_benign | 0.2544 | benign | -0.622 | Destabilizing | 0.97 | D | 0.625 | neutral | None | None | None | None | I |
| R/S | 0.9381 | likely_pathogenic | 0.915 | pathogenic | -1.43 | Destabilizing | 0.984 | D | 0.608 | neutral | N | 0.405870016 | None | None | I |
| R/T | 0.8395 | likely_pathogenic | 0.77 | pathogenic | -1.011 | Destabilizing | 0.985 | D | 0.63 | neutral | None | None | None | None | I |
| R/V | 0.8931 | likely_pathogenic | 0.8503 | pathogenic | -0.281 | Destabilizing | 0.996 | D | 0.651 | neutral | None | None | None | None | I |
| R/W | 0.6843 | likely_pathogenic | 0.6184 | pathogenic | 0.076 | Stabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| R/Y | 0.9169 | likely_pathogenic | 0.8875 | pathogenic | 0.275 | Stabilizing | 0.999 | D | 0.725 | prob.delet. | 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.