Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18476 | 55651;55652;55653 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| N2AB | 16835 | 50728;50729;50730 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| N2A | 15908 | 47947;47948;47949 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| N2B | 9411 | 28456;28457;28458 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| Novex-1 | 9536 | 28831;28832;28833 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| Novex-2 | 9603 | 29032;29033;29034 | chr2:178601664;178601663;178601662 | chr2:179466391;179466390;179466389 |
| 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/I | rs780649835  |
-0.078 | 0.997 | D | 0.731 | 0.524 | 0.794752769089 | gnomAD-2.1.1 | 8.58E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 7.55E-05 | None | 0 | 0 | 0 |
| V/I | rs780649835 |
-0.078 | 0.997 | D | 0.731 | 0.524 | 0.794752769089 | gnomAD-4.0.0 | 1.38402E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.4373E-05 | 0 |
| V/L | rs780649835 |
-0.066 | 0.997 | D | 0.765 | 0.718 | 0.852036063836 | gnomAD-2.1.1 | 4.29E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.28E-06 | 0 |
| V/L | rs780649835 |
-0.066 | 0.997 | D | 0.765 | 0.718 | 0.852036063836 | gnomAD-4.0.0 | 6.92008E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.03426E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.9495 | likely_pathogenic | 0.9633 | pathogenic | -1.75 | Destabilizing | 0.999 | D | 0.761 | deleterious | D | 0.596694858 | None | None | I |
| V/C | 0.9877 | likely_pathogenic | 0.989 | pathogenic | -1.573 | Destabilizing | 1.0 | D | 0.848 | deleterious | None | None | None | None | I |
| V/D | 0.9966 | likely_pathogenic | 0.9983 | pathogenic | -2.957 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | D | 0.597300271 | None | None | I |
| V/E | 0.9925 | likely_pathogenic | 0.9961 | pathogenic | -2.921 | Highly Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| V/F | 0.9786 | likely_pathogenic | 0.983 | pathogenic | -1.362 | Destabilizing | 1.0 | D | 0.843 | deleterious | D | 0.596694858 | None | None | I |
| V/G | 0.9542 | likely_pathogenic | 0.9718 | pathogenic | -2.082 | Highly Destabilizing | 1.0 | D | 0.786 | deleterious | D | 0.597300271 | None | None | I |
| V/H | 0.999 | likely_pathogenic | 0.9994 | pathogenic | -1.616 | Destabilizing | 1.0 | D | 0.827 | deleterious | None | None | None | None | I |
| V/I | 0.1786 | likely_benign | 0.1794 | benign | -0.895 | Destabilizing | 0.997 | D | 0.731 | prob.delet. | D | 0.527805048 | None | None | I |
| V/K | 0.9962 | likely_pathogenic | 0.998 | pathogenic | -1.554 | Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | I |
| V/L | 0.9434 | likely_pathogenic | 0.9525 | pathogenic | -0.895 | Destabilizing | 0.997 | D | 0.765 | deleterious | D | 0.594676815 | None | None | I |
| V/M | 0.938 | likely_pathogenic | 0.9518 | pathogenic | -0.783 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
| V/N | 0.9875 | likely_pathogenic | 0.9931 | pathogenic | -1.652 | Destabilizing | 1.0 | D | 0.835 | deleterious | None | None | None | None | I |
| V/P | 0.9918 | likely_pathogenic | 0.9939 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | I |
| V/Q | 0.9953 | likely_pathogenic | 0.9974 | pathogenic | -1.832 | Destabilizing | 1.0 | D | 0.837 | deleterious | None | None | None | None | I |
| V/R | 0.9936 | likely_pathogenic | 0.9964 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| V/S | 0.9762 | likely_pathogenic | 0.9854 | pathogenic | -2.025 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | None | None | None | None | I |
| V/T | 0.9273 | likely_pathogenic | 0.954 | pathogenic | -1.894 | Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | I |
| V/W | 0.9997 | likely_pathogenic | 0.9998 | pathogenic | -1.692 | Destabilizing | 1.0 | D | 0.796 | deleterious | None | None | None | None | I |
| V/Y | 0.9969 | likely_pathogenic | 0.9979 | pathogenic | -1.393 | Destabilizing | 1.0 | D | 0.851 | 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.