Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35956 | 108091;108092;108093 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| N2AB | 34315 | 103168;103169;103170 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| N2A | 33388 | 100387;100388;100389 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| N2B | 26891 | 80896;80897;80898 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| Novex-1 | 27016 | 81271;81272;81273 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| Novex-2 | 27083 | 81472;81473;81474 | chr2:178527122;178527121;178527120 | chr2:179391849;179391848;179391847 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | rs267607156  |
-1.745 | 1.0 | D | 0.895 | 0.788 | 0.873153760803 |
Hackman (2002)
Rudloff (2015)
| None |
TMD 
LGMD2J
|
het | None | -0.747(OBSL1) -0.71(OBSCN) | N | Genetic analysis of single FRA family; co-segregates within family (n = 3, 3 affected (7 total)); Severe misfolding of domain; eliminates binding to OBSCN-Ig1; low expression; monomeric | None | None | None | None | None | None | None | None | None | None | None |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9673 | likely_pathogenic | 0.9682 | pathogenic | -2.635 | Highly Destabilizing | 0.999 | D | 0.744 | deleterious | None | None | None | -0.518(OBSL1) -0.46(OBSCN) | N |
| L/C | 0.9697 | likely_pathogenic | 0.972 | pathogenic | -1.938 | Destabilizing | 1.0 | D | 0.849 | deleterious | None | None | None | -1.327(OBSL1) -0.524(OBSCN) | N |
| L/D | 0.9997 | likely_pathogenic | 0.9996 | pathogenic | -3.418 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | -0.974(OBSL1) -0.533(OBSCN) | N |
| L/E | 0.9977 | likely_pathogenic | 0.9975 | pathogenic | -3.084 | Highly Destabilizing | 1.0 | D | 0.882 | deleterious | None | None | None | -1.108(OBSL1) -0.642(OBSCN) | N |
| L/F | 0.6415 | likely_pathogenic | 0.6308 | pathogenic | -1.597 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | -1.137(OBSL1) -1.341(OBSCN) | N |
| L/G | 0.9959 | likely_pathogenic | 0.9958 | pathogenic | -3.258 | Highly Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | -0.422(OBSL1) -0.347(OBSCN) | N |
| L/H | 0.993 | likely_pathogenic | 0.9922 | pathogenic | -3.027 | Highly Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | -0.803(OBSL1) -0.361(OBSCN) | N |
| L/I | 0.3794 | ambiguous | 0.3817 | ambiguous | -0.758 | Destabilizing | 0.999 | D | 0.638 | neutral | None | None | None | -0.876(OBSL1) -0.843(OBSCN) | N |
| L/K | 0.9948 | likely_pathogenic | 0.9941 | pathogenic | -2.107 | Highly Destabilizing | 1.0 | D | 0.879 | deleterious | None | None | None | -1.218(OBSL1) -0.333(OBSCN) | N |
| L/M | 0.4052 | ambiguous | 0.4059 | ambiguous | -0.948 | Destabilizing | 1.0 | D | 0.78 | deleterious | D | 0.542120186 | None | -1.366(OBSL1) -0.994(OBSCN) | N |
| L/N | 0.9983 | likely_pathogenic | 0.9979 | pathogenic | -2.861 | Highly Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | -0.694(OBSL1) -0.253(OBSCN) | N |
| L/P | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -1.375 | Destabilizing | 1.0 | D | 0.895 | deleterious | D | 0.540678609 | None | -0.747(OBSL1) -0.71(OBSCN) | N |
| L/Q | 0.9897 | likely_pathogenic | 0.9886 | pathogenic | -2.47 | Highly Destabilizing | 1.0 | D | 0.899 | deleterious | D | 0.570139169 | None | -0.858(OBSL1) -0.347(OBSCN) | N |
| L/R | 0.987 | likely_pathogenic | 0.9868 | pathogenic | -2.255 | Highly Destabilizing | 1.0 | D | 0.893 | deleterious | D | 0.570139169 | None | -1.249(OBSL1) -0.304(OBSCN) | N |
| L/S | 0.997 | likely_pathogenic | 0.9968 | pathogenic | -3.413 | Highly Destabilizing | 1.0 | D | 0.876 | deleterious | None | None | None | -0.51(OBSL1) 0.133(OBSCN) | N |
| L/T | 0.9897 | likely_pathogenic | 0.9888 | pathogenic | -2.902 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | -0.667(OBSL1) -0.007(OBSCN) | N |
| L/V | 0.4531 | ambiguous | 0.4759 | ambiguous | -1.375 | Destabilizing | 0.999 | D | 0.645 | neutral | D | 0.529029134 | None | -0.747(OBSL1) -0.71(OBSCN) | N |
| L/W | 0.9711 | likely_pathogenic | 0.9678 | pathogenic | -2.001 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | -1.653(OBSL1) -1.838(OBSCN) | N |
| L/Y | 0.976 | likely_pathogenic | 0.975 | pathogenic | -1.771 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | -1.185(OBSL1) -1.367(OBSCN) | 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.