Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31024 | 93295;93296;93297 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| N2AB | 29383 | 88372;88373;88374 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| N2A | 28456 | 85591;85592;85593 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| N2B | 21959 | 66100;66101;66102 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| Novex-1 | 22084 | 66475;66476;66477 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| Novex-2 | 22151 | 66676;66677;66678 | chr2:178548556;178548555;178548554 | chr2:179413283;179413282;179413281 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs887995092  |
None | 0.025 | N | 0.191 | 0.078 | 0.218845423259 | gnomAD-4.0.0 | 5.47347E-06 | None | None | None | None | N | None | 5.97586E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49727E-06 | 0 | 1.65651E-05 |
| T/I | None | None | 0.97 | D | 0.693 | 0.362 | 0.40032279838 | gnomAD-4.0.0 | 1.5911E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85806E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0804 | likely_benign | 0.0732 | benign | -0.595 | Destabilizing | 0.025 | N | 0.191 | neutral | N | 0.492239137 | None | None | N |
| T/C | 0.3353 | likely_benign | 0.2823 | benign | -0.398 | Destabilizing | 0.998 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/D | 0.5207 | ambiguous | 0.3728 | ambiguous | 0.063 | Stabilizing | 0.956 | D | 0.674 | neutral | None | None | None | None | N |
| T/E | 0.4385 | ambiguous | 0.3128 | benign | 0.066 | Stabilizing | 0.86 | D | 0.641 | neutral | None | None | None | None | N |
| T/F | 0.2501 | likely_benign | 0.1906 | benign | -0.827 | Destabilizing | 0.978 | D | 0.782 | deleterious | None | None | None | None | N |
| T/G | 0.2183 | likely_benign | 0.1691 | benign | -0.817 | Destabilizing | 0.754 | D | 0.653 | neutral | None | None | None | None | N |
| T/H | 0.2454 | likely_benign | 0.1891 | benign | -0.935 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| T/I | 0.142 | likely_benign | 0.1115 | benign | -0.1 | Destabilizing | 0.97 | D | 0.693 | prob.neutral | D | 0.522388686 | None | None | N |
| T/K | 0.3063 | likely_benign | 0.2106 | benign | -0.448 | Destabilizing | 0.86 | D | 0.641 | neutral | None | None | None | None | N |
| T/L | 0.0943 | likely_benign | 0.0771 | benign | -0.1 | Destabilizing | 0.86 | D | 0.585 | neutral | None | None | None | None | N |
| T/M | 0.0966 | likely_benign | 0.0883 | benign | -0.161 | Destabilizing | 0.998 | D | 0.731 | prob.delet. | None | None | None | None | N |
| T/N | 0.1317 | likely_benign | 0.1066 | benign | -0.415 | Destabilizing | 0.942 | D | 0.565 | neutral | N | 0.47760021 | None | None | N |
| T/P | 0.4086 | ambiguous | 0.291 | benign | -0.234 | Destabilizing | 0.97 | D | 0.735 | prob.delet. | N | 0.513101158 | None | None | N |
| T/Q | 0.2625 | likely_benign | 0.202 | benign | -0.482 | Destabilizing | 0.956 | D | 0.745 | deleterious | None | None | None | None | N |
| T/R | 0.2477 | likely_benign | 0.1748 | benign | -0.233 | Destabilizing | 0.956 | D | 0.742 | deleterious | None | None | None | None | N |
| T/S | 0.1 | likely_benign | 0.0848 | benign | -0.656 | Destabilizing | 0.058 | N | 0.197 | neutral | N | 0.509840676 | None | None | N |
| T/V | 0.1123 | likely_benign | 0.095 | benign | -0.234 | Destabilizing | 0.86 | D | 0.492 | neutral | None | None | None | None | N |
| T/W | 0.6661 | likely_pathogenic | 0.5699 | pathogenic | -0.864 | Destabilizing | 0.998 | D | 0.753 | deleterious | None | None | None | None | N |
| T/Y | 0.303 | likely_benign | 0.2298 | benign | -0.575 | Destabilizing | 0.993 | D | 0.783 | 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.