Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32476 | 97651;97652;97653 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| N2AB | 30835 | 92728;92729;92730 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| N2A | 29908 | 89947;89948;89949 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| N2B | 23411 | 70456;70457;70458 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| Novex-1 | 23536 | 70831;70832;70833 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| Novex-2 | 23603 | 71032;71033;71034 | chr2:178542330;178542329;178542328 | chr2:179407057;179407056;179407055 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs760169773  |
-1.877 | 1.0 | D | 0.778 | 0.64 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| A/T | rs760169773 |
-1.877 | 1.0 | D | 0.778 | 0.64 | None | 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 |
| A/T | rs760169773 |
-1.877 | 1.0 | D | 0.778 | 0.64 | None | gnomAD-4.0.0 | 1.30189E-05 | None | None | None | None | N | None | 1.33533E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52606E-05 | 0 | 3.2039E-05 |
| A/V | None | None | 1.0 | D | 0.711 | 0.613 | 0.762146552022 | gnomAD-4.0.0 | 1.5928E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78381E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7905 | likely_pathogenic | 0.8324 | pathogenic | -1.916 | Destabilizing | 1.0 | D | 0.775 | deleterious | None | None | None | None | N |
| A/D | 0.9972 | likely_pathogenic | 0.9973 | pathogenic | -3.012 | Highly Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | N |
| A/E | 0.9952 | likely_pathogenic | 0.9954 | pathogenic | -2.792 | Highly Destabilizing | 1.0 | D | 0.788 | deleterious | D | 0.581158944 | None | None | N |
| A/F | 0.9876 | likely_pathogenic | 0.9905 | pathogenic | -0.707 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| A/G | 0.3272 | likely_benign | 0.313 | benign | -2.086 | Highly Destabilizing | 1.0 | D | 0.64 | neutral | D | 0.549670468 | None | None | N |
| A/H | 0.9962 | likely_pathogenic | 0.9972 | pathogenic | -1.965 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| A/I | 0.9748 | likely_pathogenic | 0.9754 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.798 | deleterious | None | None | None | None | N |
| A/K | 0.9987 | likely_pathogenic | 0.9989 | pathogenic | -1.402 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | N |
| A/L | 0.9283 | likely_pathogenic | 0.9305 | pathogenic | -0.523 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| A/M | 0.9564 | likely_pathogenic | 0.9564 | pathogenic | -1.133 | Destabilizing | 1.0 | D | 0.82 | deleterious | None | None | None | None | N |
| A/N | 0.9877 | likely_pathogenic | 0.9891 | pathogenic | -1.91 | Destabilizing | 1.0 | D | 0.824 | deleterious | None | None | None | None | N |
| A/P | 0.8523 | likely_pathogenic | 0.9243 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.803 | deleterious | D | 0.557939354 | None | None | N |
| A/Q | 0.9881 | likely_pathogenic | 0.9894 | pathogenic | -1.666 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| A/R | 0.995 | likely_pathogenic | 0.9957 | pathogenic | -1.471 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/S | 0.2923 | likely_benign | 0.2825 | benign | -2.228 | Highly Destabilizing | 1.0 | D | 0.641 | neutral | D | 0.529159903 | None | None | N |
| A/T | 0.781 | likely_pathogenic | 0.7684 | pathogenic | -1.901 | Destabilizing | 1.0 | D | 0.778 | deleterious | D | 0.568535191 | None | None | N |
| A/V | 0.8647 | likely_pathogenic | 0.8643 | pathogenic | -0.874 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | D | 0.556925396 | None | None | N |
| A/W | 0.9991 | likely_pathogenic | 0.9993 | pathogenic | -1.317 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| A/Y | 0.9954 | likely_pathogenic | 0.9966 | pathogenic | -1.004 | Destabilizing | 1.0 | D | 0.848 | 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.