Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22835 | 68728;68729;68730 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| N2AB | 21194 | 63805;63806;63807 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| N2A | 20267 | 61024;61025;61026 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| N2B | 13770 | 41533;41534;41535 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| Novex-1 | 13895 | 41908;41909;41910 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| Novex-2 | 13962 | 42109;42110;42111 | chr2:178578012;178578011;178578010 | chr2:179442739;179442738;179442737 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs750857565  |
-1.143 | 0.029 | N | 0.184 | 0.126 | 0.185906805712 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 0 | 1.16185E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| P/A | rs750857565 |
-1.143 | 0.029 | N | 0.184 | 0.126 | 0.185906805712 | gnomAD-4.0.0 | 6.37154E-06 | None | None | None | None | I | None | 0 | 9.15122E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| P/H | rs1187118062 |
-1.121 | 0.998 | N | 0.589 | 0.323 | 0.393775345888 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| P/H | rs1187118062 |
-1.121 | 0.998 | N | 0.589 | 0.323 | 0.393775345888 | gnomAD-4.0.0 | 1.36904E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79946E-06 | 0 | 0 |
| P/L | None | None | 0.842 | N | 0.64 | 0.249 | 0.459463830659 | gnomAD-4.0.0 | 6.8452E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99729E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0801 | likely_benign | 0.069 | benign | -1.106 | Destabilizing | 0.029 | N | 0.184 | neutral | N | 0.495348439 | None | None | I |
| P/C | 0.4681 | ambiguous | 0.3959 | ambiguous | -0.796 | Destabilizing | 0.998 | D | 0.648 | neutral | None | None | None | None | I |
| P/D | 0.769 | likely_pathogenic | 0.6854 | pathogenic | -0.879 | Destabilizing | 0.876 | D | 0.517 | neutral | None | None | None | None | I |
| P/E | 0.5809 | likely_pathogenic | 0.4849 | ambiguous | -0.949 | Destabilizing | 0.876 | D | 0.501 | neutral | None | None | None | None | I |
| P/F | 0.5697 | likely_pathogenic | 0.4834 | ambiguous | -0.989 | Destabilizing | 0.994 | D | 0.658 | prob.neutral | None | None | None | None | I |
| P/G | 0.3585 | ambiguous | 0.2959 | benign | -1.335 | Destabilizing | 0.009 | N | 0.325 | neutral | None | None | None | None | I |
| P/H | 0.346 | ambiguous | 0.2755 | benign | -0.792 | Destabilizing | 0.998 | D | 0.589 | neutral | N | 0.491164425 | None | None | I |
| P/I | 0.4657 | ambiguous | 0.4013 | ambiguous | -0.616 | Destabilizing | 0.981 | D | 0.679 | prob.neutral | None | None | None | None | I |
| P/K | 0.5791 | likely_pathogenic | 0.4898 | ambiguous | -0.979 | Destabilizing | 0.876 | D | 0.522 | neutral | None | None | None | None | I |
| P/L | 0.2337 | likely_benign | 0.18 | benign | -0.616 | Destabilizing | 0.842 | D | 0.64 | neutral | N | 0.462118258 | None | None | I |
| P/M | 0.3931 | ambiguous | 0.3197 | benign | -0.48 | Destabilizing | 0.998 | D | 0.589 | neutral | None | None | None | None | I |
| P/N | 0.513 | ambiguous | 0.4176 | ambiguous | -0.684 | Destabilizing | 0.961 | D | 0.619 | neutral | None | None | None | None | I |
| P/Q | 0.344 | ambiguous | 0.2683 | benign | -0.939 | Destabilizing | 0.981 | D | 0.543 | neutral | None | None | None | None | I |
| P/R | 0.4167 | ambiguous | 0.3283 | benign | -0.362 | Destabilizing | 0.974 | D | 0.598 | neutral | N | 0.469514998 | None | None | I |
| P/S | 0.1762 | likely_benign | 0.1432 | benign | -1.124 | Destabilizing | 0.172 | N | 0.251 | neutral | N | 0.504642713 | None | None | I |
| P/T | 0.1641 | likely_benign | 0.1337 | benign | -1.095 | Destabilizing | 0.728 | D | 0.527 | neutral | N | 0.473033717 | None | None | I |
| P/V | 0.2963 | likely_benign | 0.2497 | benign | -0.743 | Destabilizing | 0.876 | D | 0.566 | neutral | None | None | None | None | I |
| P/W | 0.7566 | likely_pathogenic | 0.68 | pathogenic | -1.074 | Destabilizing | 0.998 | D | 0.701 | prob.delet. | None | None | None | None | I |
| P/Y | 0.548 | ambiguous | 0.4681 | ambiguous | -0.816 | Destabilizing | 0.994 | D | 0.662 | prob.neutral | None | None | None | None | I |
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.