Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26270 | 79033;79034;79035 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| N2AB | 24629 | 74110;74111;74112 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| N2A | 23702 | 71329;71330;71331 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| N2B | 17205 | 51838;51839;51840 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| Novex-1 | 17330 | 52213;52214;52215 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| Novex-2 | 17397 | 52414;52415;52416 | chr2:178567324;178567323;178567322 | chr2:179432051;179432050;179432049 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/I | None | None | 1.0 | D | 0.725 | 0.693 | 0.808133268326 | gnomAD-4.0.0 | 2.75281E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.60717E-06 | 0 | 0 |
| N/S | rs1239041708  |
None | 0.999 | N | 0.575 | 0.623 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs1239041708 |
None | 0.999 | N | 0.575 | 0.623 | None | gnomAD-4.0.0 | 1.246E-06 | None | None | None | None | I | None | 0 | 1.71415E-05 | None | 0 | 0 | None | 0 | 0 | 8.49706E-07 | 0 | 0 |
| N/T | rs1239041708 |
None | 0.999 | D | 0.721 | 0.718 | 0.503002171853 | gnomAD-4.0.0 | 6.88203E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01791E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9923 | likely_pathogenic | 0.9912 | pathogenic | -0.624 | Destabilizing | 1.0 | D | 0.772 | deleterious | None | None | None | None | I |
| N/C | 0.9186 | likely_pathogenic | 0.9086 | pathogenic | 0.081 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/D | 0.9927 | likely_pathogenic | 0.9898 | pathogenic | -0.909 | Destabilizing | 0.999 | D | 0.615 | neutral | D | 0.557361064 | None | None | I |
| N/E | 0.9989 | likely_pathogenic | 0.9987 | pathogenic | -0.915 | Destabilizing | 0.999 | D | 0.729 | prob.delet. | None | None | None | None | I |
| N/F | 0.9991 | likely_pathogenic | 0.9988 | pathogenic | -1.051 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| N/G | 0.983 | likely_pathogenic | 0.9814 | pathogenic | -0.81 | Destabilizing | 0.999 | D | 0.551 | neutral | None | None | None | None | I |
| N/H | 0.973 | likely_pathogenic | 0.9663 | pathogenic | -0.98 | Destabilizing | 1.0 | D | 0.755 | deleterious | D | 0.540524256 | None | None | I |
| N/I | 0.9928 | likely_pathogenic | 0.9907 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | D | 0.558882001 | None | None | I |
| N/K | 0.9991 | likely_pathogenic | 0.9988 | pathogenic | -0.04 | Destabilizing | 1.0 | D | 0.753 | deleterious | D | 0.558121532 | None | None | I |
| N/L | 0.9798 | likely_pathogenic | 0.9764 | pathogenic | -0.202 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | I |
| N/M | 0.9926 | likely_pathogenic | 0.9912 | pathogenic | 0.515 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | None | None | None | None | I |
| N/P | 0.997 | likely_pathogenic | 0.9963 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| N/Q | 0.9985 | likely_pathogenic | 0.9982 | pathogenic | -0.852 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| N/R | 0.9978 | likely_pathogenic | 0.997 | pathogenic | 0.111 | Stabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| N/S | 0.7197 | likely_pathogenic | 0.7024 | pathogenic | -0.442 | Destabilizing | 0.999 | D | 0.575 | neutral | N | 0.502692677 | None | None | I |
| N/T | 0.93 | likely_pathogenic | 0.9207 | pathogenic | -0.312 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | D | 0.539510298 | None | None | I |
| N/V | 0.9867 | likely_pathogenic | 0.9831 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
| N/W | 0.9998 | likely_pathogenic | 0.9997 | pathogenic | -0.95 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| N/Y | 0.9944 | likely_pathogenic | 0.993 | pathogenic | -0.656 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | D | 0.558628511 | 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.