Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22878 | 68857;68858;68859 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| N2AB | 21237 | 63934;63935;63936 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| N2A | 20310 | 61153;61154;61155 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| N2B | 13813 | 41662;41663;41664 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| Novex-1 | 13938 | 42037;42038;42039 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| Novex-2 | 14005 | 42238;42239;42240 | chr2:178577794;178577793;178577792 | chr2:179442521;179442520;179442519 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | None | None | 0.998 | D | 0.647 | 0.674 | 0.72024247472 | gnomAD-4.0.0 | 6.84482E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99683E-07 | 0 | 0 |
| V/M | rs764263517  |
-0.765 | 0.999 | N | 0.751 | 0.483 | 0.625091758369 | gnomAD-2.1.1 | 1.09121E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.67E-05 | 2.32587E-04 | 0 |
| V/M | rs764263517 |
-0.765 | 0.999 | N | 0.751 | 0.483 | 0.625091758369 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.88324E-04 | 0 | 1.47E-05 | 0 | 0 |
| V/M | rs764263517 |
-0.765 | 0.999 | N | 0.751 | 0.483 | 0.625091758369 | gnomAD-4.0.0 | 4.2785E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.12832E-05 | 0 | 5.42647E-05 | 0 | 4.80538E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.8681 | likely_pathogenic | 0.8482 | pathogenic | -2.271 | Highly Destabilizing | 0.998 | D | 0.647 | neutral | D | 0.564683623 | None | None | N |
| V/C | 0.9787 | likely_pathogenic | 0.9767 | pathogenic | -1.576 | Destabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | N |
| V/D | 0.9991 | likely_pathogenic | 0.9989 | pathogenic | -3.302 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/E | 0.9957 | likely_pathogenic | 0.9952 | pathogenic | -2.965 | Highly Destabilizing | 1.0 | D | 0.869 | deleterious | D | 0.565444092 | None | None | N |
| V/F | 0.9337 | likely_pathogenic | 0.9317 | pathogenic | -1.332 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | N |
| V/G | 0.9751 | likely_pathogenic | 0.9695 | pathogenic | -2.892 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.565444092 | None | None | N |
| V/H | 0.999 | likely_pathogenic | 0.9988 | pathogenic | -2.912 | Highly Destabilizing | 1.0 | D | 0.872 | deleterious | None | None | None | None | N |
| V/I | 0.0787 | likely_benign | 0.0833 | benign | -0.45 | Destabilizing | 0.813 | D | 0.312 | neutral | None | None | None | None | N |
| V/K | 0.9965 | likely_pathogenic | 0.9961 | pathogenic | -1.843 | Destabilizing | 1.0 | D | 0.869 | deleterious | None | None | None | None | N |
| V/L | 0.4749 | ambiguous | 0.5096 | ambiguous | -0.45 | Destabilizing | 0.981 | D | 0.605 | neutral | N | 0.48278904 | None | None | N |
| V/M | 0.7419 | likely_pathogenic | 0.74 | pathogenic | -0.681 | Destabilizing | 0.999 | D | 0.751 | deleterious | N | 0.517372297 | None | None | N |
| V/N | 0.9969 | likely_pathogenic | 0.9965 | pathogenic | -2.613 | Highly Destabilizing | 1.0 | D | 0.881 | deleterious | None | None | None | None | N |
| V/P | 0.9876 | likely_pathogenic | 0.9858 | pathogenic | -1.04 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| V/Q | 0.9954 | likely_pathogenic | 0.9948 | pathogenic | -2.197 | Highly Destabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| V/R | 0.9932 | likely_pathogenic | 0.9923 | pathogenic | -2.067 | Highly Destabilizing | 1.0 | D | 0.887 | deleterious | None | None | None | None | N |
| V/S | 0.9831 | likely_pathogenic | 0.9792 | pathogenic | -3.069 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | None | N |
| V/T | 0.8991 | likely_pathogenic | 0.8899 | pathogenic | -2.564 | Highly Destabilizing | 0.998 | D | 0.704 | prob.neutral | None | None | None | None | N |
| V/W | 0.9987 | likely_pathogenic | 0.9985 | pathogenic | -1.91 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/Y | 0.996 | likely_pathogenic | 0.9956 | pathogenic | -1.582 | Destabilizing | 1.0 | D | 0.833 | deleterious | 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.