Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21535 | 64828;64829;64830 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| N2AB | 19894 | 59905;59906;59907 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| N2A | 18967 | 57124;57125;57126 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| N2B | 12470 | 37633;37634;37635 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| Novex-1 | 12595 | 38008;38009;38010 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| Novex-2 | 12662 | 38209;38210;38211 | chr2:178585141;178585140;178585139 | chr2:179449868;179449867;179449866 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/S | rs746465231  |
-0.416 | 0.999 | D | 0.842 | 0.606 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 6.47E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| G/S | rs746465231 |
-0.416 | 0.999 | D | 0.842 | 0.606 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| G/S | rs746465231 |
-0.416 | 0.999 | D | 0.842 | 0.606 | None | gnomAD-4.0.0 | 1.8597E-06 | None | None | None | None | N | None | 1.33586E-05 | 1.66733E-05 | None | 0 | 0 | None | 0 | 0 | 8.47853E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| G/A | 0.2653 | likely_benign | 0.2174 | benign | -0.336 | Destabilizing | 0.995 | D | 0.749 | deleterious | D | 0.591649751 | None | None | N |
| G/C | 0.4449 | ambiguous | 0.3657 | ambiguous | -0.387 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.63185352 | None | None | N |
| G/D | 0.4195 | ambiguous | 0.3707 | ambiguous | -0.298 | Destabilizing | 0.604 | D | 0.717 | prob.delet. | D | 0.599411189 | None | None | N |
| G/E | 0.6896 | likely_pathogenic | 0.6131 | pathogenic | -0.288 | Destabilizing | 0.998 | D | 0.792 | deleterious | None | None | None | None | N |
| G/F | 0.9161 | likely_pathogenic | 0.8896 | pathogenic | -0.583 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| G/H | 0.8167 | likely_pathogenic | 0.7504 | pathogenic | -1.101 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| G/I | 0.8536 | likely_pathogenic | 0.8043 | pathogenic | 0.245 | Stabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| G/K | 0.898 | likely_pathogenic | 0.853 | pathogenic | -0.605 | Destabilizing | 0.999 | D | 0.787 | deleterious | None | None | None | None | N |
| G/L | 0.8249 | likely_pathogenic | 0.7663 | pathogenic | 0.245 | Stabilizing | 0.999 | D | 0.758 | deleterious | None | None | None | None | N |
| G/M | 0.8569 | likely_pathogenic | 0.8062 | pathogenic | 0.145 | Stabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | N |
| G/N | 0.5456 | ambiguous | 0.4745 | ambiguous | -0.376 | Destabilizing | 0.998 | D | 0.835 | deleterious | None | None | None | None | N |
| G/P | 0.9915 | likely_pathogenic | 0.9916 | pathogenic | 0.095 | Stabilizing | 0.999 | D | 0.777 | deleterious | None | None | None | None | N |
| G/Q | 0.721 | likely_pathogenic | 0.6526 | pathogenic | -0.392 | Destabilizing | 0.999 | D | 0.782 | deleterious | None | None | None | None | N |
| G/R | 0.7832 | likely_pathogenic | 0.7306 | pathogenic | -0.586 | Destabilizing | 0.999 | D | 0.783 | deleterious | D | 0.631651716 | None | None | N |
| G/S | 0.1735 | likely_benign | 0.1388 | benign | -0.752 | Destabilizing | 0.999 | D | 0.842 | deleterious | D | 0.631248107 | None | None | N |
| G/T | 0.487 | ambiguous | 0.4028 | ambiguous | -0.631 | Destabilizing | 0.999 | D | 0.789 | deleterious | None | None | None | None | N |
| G/V | 0.7427 | likely_pathogenic | 0.6781 | pathogenic | 0.095 | Stabilizing | 0.999 | D | 0.747 | deleterious | D | 0.63185352 | None | None | N |
| G/W | 0.8965 | likely_pathogenic | 0.8659 | pathogenic | -1.09 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| G/Y | 0.8646 | likely_pathogenic | 0.8222 | pathogenic | -0.535 | Destabilizing | 1.0 | D | 0.779 | 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.