Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23035 | 69328;69329;69330 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| N2AB | 21394 | 64405;64406;64407 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| N2A | 20467 | 61624;61625;61626 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| N2B | 13970 | 42133;42134;42135 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| Novex-1 | 14095 | 42508;42509;42510 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| Novex-2 | 14162 | 42709;42710;42711 | chr2:178577232;178577231;178577230 | chr2:179441959;179441958;179441957 |
| 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/E | rs1466022888  |
-1.666 | 0.994 | D | 0.867 | 0.585 | 0.782406081309 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 0 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66556E-04 |
| V/E | rs1466022888 |
-1.666 | 0.994 | D | 0.867 | 0.585 | 0.782406081309 | gnomAD-4.0.0 | 3.18537E-06 | None | None | None | None | N | None | 0 | 2.28822E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02737E-05 |
| V/I | rs200878877 |
-0.356 | 0.825 | N | 0.565 | 0.156 | None | gnomAD-2.1.1 | 8.96E-05 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.88265E-04 | 0 |
| V/I | rs200878877 |
-0.356 | 0.825 | N | 0.565 | 0.156 | None | gnomAD-3.1.2 | 7.25E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.61941E-04 | 0 | 0 |
| V/I | rs200878877 |
-0.356 | 0.825 | N | 0.565 | 0.156 | None | gnomAD-4.0.0 | 8.18471E-05 | None | None | None | None | N | None | 0 | 1.6695E-05 | None | 0 | 0 | None | 3.1294E-05 | 0 | 9.75011E-05 | 1.09832E-05 | 2.0828E-04 |
| V/L | rs200878877 |
-0.358 | 0.067 | N | 0.306 | 0.172 | 0.286848849266 | gnomAD-2.1.1 | 2.42E-05 | None | None | None | None | N | None | 0 | 1.74338E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs200878877 |
-0.358 | 0.067 | N | 0.306 | 0.172 | 0.286848849266 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs200878877 |
-0.358 | 0.067 | N | 0.306 | 0.172 | 0.286848849266 | gnomAD-4.0.0 | 4.34037E-06 | None | None | None | None | N | None | 1.33693E-05 | 1.0017E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7912 | likely_pathogenic | 0.8234 | pathogenic | -2.124 | Highly Destabilizing | 0.958 | D | 0.648 | neutral | N | 0.503531008 | None | None | N |
| V/C | 0.9375 | likely_pathogenic | 0.945 | pathogenic | -1.71 | Destabilizing | 1.0 | D | 0.814 | deleterious | None | None | None | None | N |
| V/D | 0.9946 | likely_pathogenic | 0.9973 | pathogenic | -2.618 | Highly Destabilizing | 0.998 | D | 0.865 | deleterious | None | None | None | None | N |
| V/E | 0.9882 | likely_pathogenic | 0.9935 | pathogenic | -2.367 | Highly Destabilizing | 0.994 | D | 0.867 | deleterious | D | 0.522142242 | None | None | N |
| V/F | 0.7763 | likely_pathogenic | 0.8268 | pathogenic | -1.257 | Destabilizing | 0.991 | D | 0.823 | deleterious | None | None | None | None | N |
| V/G | 0.8555 | likely_pathogenic | 0.9041 | pathogenic | -2.709 | Highly Destabilizing | 0.994 | D | 0.875 | deleterious | D | 0.522142242 | None | None | N |
| V/H | 0.9962 | likely_pathogenic | 0.9973 | pathogenic | -2.488 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | None | N |
| V/I | 0.1111 | likely_benign | 0.1057 | benign | -0.475 | Destabilizing | 0.825 | D | 0.565 | neutral | N | 0.456100642 | None | None | N |
| V/K | 0.9906 | likely_pathogenic | 0.9934 | pathogenic | -1.794 | Destabilizing | 0.995 | D | 0.861 | deleterious | None | None | None | None | N |
| V/L | 0.4918 | ambiguous | 0.5114 | ambiguous | -0.475 | Destabilizing | 0.067 | N | 0.306 | neutral | N | 0.442243807 | None | None | N |
| V/M | 0.5774 | likely_pathogenic | 0.6311 | pathogenic | -0.552 | Destabilizing | 0.991 | D | 0.739 | prob.delet. | None | None | None | None | N |
| V/N | 0.9815 | likely_pathogenic | 0.9896 | pathogenic | -2.188 | Highly Destabilizing | 0.998 | D | 0.875 | deleterious | None | None | None | None | N |
| V/P | 0.9918 | likely_pathogenic | 0.9926 | pathogenic | -0.998 | Destabilizing | 0.998 | D | 0.855 | deleterious | None | None | None | None | N |
| V/Q | 0.9885 | likely_pathogenic | 0.993 | pathogenic | -1.963 | Destabilizing | 0.998 | D | 0.864 | deleterious | None | None | None | None | N |
| V/R | 0.9864 | likely_pathogenic | 0.9908 | pathogenic | -1.713 | Destabilizing | 0.995 | D | 0.875 | deleterious | None | None | None | None | N |
| V/S | 0.9561 | likely_pathogenic | 0.9726 | pathogenic | -2.857 | Highly Destabilizing | 0.995 | D | 0.863 | deleterious | None | None | None | None | N |
| V/T | 0.8541 | likely_pathogenic | 0.8836 | pathogenic | -2.444 | Highly Destabilizing | 0.968 | D | 0.676 | prob.neutral | None | None | None | None | N |
| V/W | 0.9968 | likely_pathogenic | 0.9975 | pathogenic | -1.79 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | N |
| V/Y | 0.9741 | likely_pathogenic | 0.9814 | pathogenic | -1.391 | Destabilizing | 0.995 | D | 0.807 | 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.