Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26478 | 79657;79658;79659 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| N2AB | 24837 | 74734;74735;74736 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| N2A | 23910 | 71953;71954;71955 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| N2B | 17413 | 52462;52463;52464 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| Novex-1 | 17538 | 52837;52838;52839 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| Novex-2 | 17605 | 53038;53039;53040 | chr2:178566700;178566699;178566698 | chr2:179431427;179431426;179431425 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs1053235966  |
None | 1.0 | N | 0.783 | 0.383 | 0.563910400117 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85894E-06 | 0 | 0 |
| Y/D | rs768735283 |
-3.206 | 0.993 | N | 0.869 | 0.539 | 0.730013675969 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/D | rs768735283 |
-3.206 | 0.993 | N | 0.869 | 0.539 | 0.730013675969 | gnomAD-4.0.0 | 1.59209E-06 | None | None | None | None | N | None | 5.65803E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4949 | ambiguous | 0.4635 | ambiguous | -2.499 | Highly Destabilizing | 0.965 | D | 0.671 | prob.neutral | None | None | None | None | N |
| Y/C | 0.1519 | likely_benign | 0.1213 | benign | -0.927 | Destabilizing | 1.0 | D | 0.783 | deleterious | N | 0.473135849 | None | None | N |
| Y/D | 0.6338 | likely_pathogenic | 0.5914 | pathogenic | -0.894 | Destabilizing | 0.993 | D | 0.869 | deleterious | N | 0.484745644 | None | None | N |
| Y/E | 0.8707 | likely_pathogenic | 0.8282 | pathogenic | -0.815 | Destabilizing | 0.995 | D | 0.784 | deleterious | None | None | None | None | N |
| Y/F | 0.0731 | likely_benign | 0.0688 | benign | -1.126 | Destabilizing | 0.996 | D | 0.529 | neutral | N | 0.432547754 | None | None | N |
| Y/G | 0.4768 | ambiguous | 0.4529 | ambiguous | -2.803 | Highly Destabilizing | 0.982 | D | 0.783 | deleterious | None | None | None | None | N |
| Y/H | 0.3035 | likely_benign | 0.2835 | benign | -1.046 | Destabilizing | 0.999 | D | 0.691 | prob.delet. | N | 0.484492155 | None | None | N |
| Y/I | 0.6021 | likely_pathogenic | 0.5186 | ambiguous | -1.575 | Destabilizing | 0.997 | D | 0.73 | deleterious | None | None | None | None | N |
| Y/K | 0.8356 | likely_pathogenic | 0.8032 | pathogenic | -1.115 | Destabilizing | 0.995 | D | 0.79 | deleterious | None | None | None | None | N |
| Y/L | 0.4659 | ambiguous | 0.4052 | ambiguous | -1.575 | Destabilizing | 0.991 | D | 0.662 | prob.neutral | None | None | None | None | N |
| Y/M | 0.7146 | likely_pathogenic | 0.6494 | pathogenic | -1.152 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| Y/N | 0.3332 | likely_benign | 0.3051 | benign | -1.334 | Destabilizing | 0.993 | D | 0.819 | deleterious | N | 0.484492155 | None | None | N |
| Y/P | 0.4765 | ambiguous | 0.4438 | ambiguous | -1.879 | Destabilizing | 0.997 | D | 0.869 | deleterious | None | None | None | None | N |
| Y/Q | 0.7396 | likely_pathogenic | 0.6929 | pathogenic | -1.339 | Destabilizing | 0.997 | D | 0.716 | prob.delet. | None | None | None | None | N |
| Y/R | 0.6902 | likely_pathogenic | 0.6499 | pathogenic | -0.56 | Destabilizing | 0.997 | D | 0.809 | deleterious | None | None | None | None | N |
| Y/S | 0.3 | likely_benign | 0.2811 | benign | -1.931 | Destabilizing | 0.787 | D | 0.566 | neutral | N | 0.516494502 | None | None | N |
| Y/T | 0.5676 | likely_pathogenic | 0.5226 | ambiguous | -1.765 | Destabilizing | 0.99 | D | 0.784 | deleterious | None | None | None | None | N |
| Y/V | 0.499 | ambiguous | 0.4359 | ambiguous | -1.879 | Destabilizing | 0.997 | D | 0.708 | prob.delet. | None | None | None | None | N |
| Y/W | 0.4496 | ambiguous | 0.4192 | ambiguous | -0.614 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | 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.