Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16626 | 50101;50102;50103 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| N2AB | 14985 | 45178;45179;45180 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| N2A | 14058 | 42397;42398;42399 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| N2B | 7561 | 22906;22907;22908 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| Novex-1 | 7686 | 23281;23282;23283 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| Novex-2 | 7753 | 23482;23483;23484 | chr2:178612845;178612844;178612843 | chr2:179477572;179477571;179477570 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/T | rs773007980  |
-1.716 | 0.998 | N | 0.679 | 0.362 | 0.384752662912 | gnomAD-2.1.1 | 7.17E-06 | None | None | None | None | N | None | 0 | 0 | None | 9.7E-05 | 5.21E-05 | None | 0 | None | 0 | 0 | 0 |
| R/T | rs773007980 |
-1.716 | 0.998 | N | 0.679 | 0.362 | 0.384752662912 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.95389E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/T | rs773007980 |
-1.716 | 0.998 | N | 0.679 | 0.362 | 0.384752662912 | gnomAD-4.0.0 | 3.84946E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.095E-05 | 4.88926E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6918 | likely_pathogenic | 0.7502 | pathogenic | -1.509 | Destabilizing | 0.992 | D | 0.634 | neutral | None | None | None | None | N |
| R/C | 0.2405 | likely_benign | 0.2469 | benign | -1.722 | Destabilizing | 1.0 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/D | 0.97 | likely_pathogenic | 0.9769 | pathogenic | -1.081 | Destabilizing | 0.999 | D | 0.712 | prob.delet. | None | None | None | None | N |
| R/E | 0.7774 | likely_pathogenic | 0.835 | pathogenic | -0.91 | Destabilizing | 0.992 | D | 0.651 | neutral | None | None | None | None | N |
| R/F | 0.7252 | likely_pathogenic | 0.7513 | pathogenic | -0.961 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| R/G | 0.6846 | likely_pathogenic | 0.7558 | pathogenic | -1.793 | Destabilizing | 0.994 | D | 0.685 | prob.neutral | D | 0.631303708 | None | None | N |
| R/H | 0.2211 | likely_benign | 0.2269 | benign | -1.893 | Destabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| R/I | 0.3825 | ambiguous | 0.4634 | ambiguous | -0.713 | Destabilizing | 0.999 | D | 0.736 | prob.delet. | N | 0.483720643 | None | None | N |
| R/K | 0.1166 | likely_benign | 0.1162 | benign | -1.462 | Destabilizing | 0.543 | D | 0.346 | neutral | N | 0.457861113 | None | None | N |
| R/L | 0.335 | likely_benign | 0.3938 | ambiguous | -0.713 | Destabilizing | 0.996 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/M | 0.4202 | ambiguous | 0.4947 | ambiguous | -1.221 | Destabilizing | 1.0 | D | 0.676 | prob.neutral | None | None | None | None | N |
| R/N | 0.9088 | likely_pathogenic | 0.925 | pathogenic | -1.319 | Destabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | N |
| R/P | 0.9923 | likely_pathogenic | 0.9952 | pathogenic | -0.965 | Destabilizing | 1.0 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/Q | 0.2187 | likely_benign | 0.2392 | benign | -1.156 | Destabilizing | 0.998 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/S | 0.7963 | likely_pathogenic | 0.8303 | pathogenic | -1.94 | Destabilizing | 0.989 | D | 0.657 | neutral | N | 0.477793083 | None | None | N |
| R/T | 0.4877 | ambiguous | 0.5618 | ambiguous | -1.595 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | N | 0.480954813 | None | None | N |
| R/V | 0.4677 | ambiguous | 0.5249 | ambiguous | -0.965 | Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| R/W | 0.3836 | ambiguous | 0.45 | ambiguous | -0.728 | Destabilizing | 1.0 | D | 0.638 | neutral | None | None | None | None | N |
| R/Y | 0.6808 | likely_pathogenic | 0.7066 | pathogenic | -0.466 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | 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.