Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19303 | 58132;58133;58134 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| N2AB | 17662 | 53209;53210;53211 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| N2A | 16735 | 50428;50429;50430 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| N2B | 10238 | 30937;30938;30939 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| Novex-1 | 10363 | 31312;31313;31314 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| Novex-2 | 10430 | 31513;31514;31515 | chr2:178594587;178594586;178594585 | chr2:179459314;179459313;179459312 |
| 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/F | rs868588764  |
None | 0.997 | D | 0.615 | 0.451 | 0.589635058153 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/M | rs1395931081 |
-1.387 | 0.997 | N | 0.615 | 0.393 | 0.542100083394 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 0 | 0 |
| L/M | rs1395931081 |
-1.387 | 0.997 | N | 0.615 | 0.393 | 0.542100083394 | gnomAD-4.0.0 | 6.84596E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16117E-05 | 0 |
| L/V | None | None | 0.198 | N | 0.293 | 0.116 | 0.27479166964 | gnomAD-4.0.0 | 2.05379E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69948E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.9483 | likely_pathogenic | 0.954 | pathogenic | -2.955 | Highly Destabilizing | 0.983 | D | 0.709 | prob.delet. | None | None | None | None | N |
| L/C | 0.9139 | likely_pathogenic | 0.9327 | pathogenic | -1.994 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| L/D | 0.9998 | likely_pathogenic | 0.9998 | pathogenic | -3.558 | Highly Destabilizing | 0.999 | D | 0.913 | deleterious | None | None | None | None | N |
| L/E | 0.9982 | likely_pathogenic | 0.9985 | pathogenic | -3.219 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| L/F | 0.7255 | likely_pathogenic | 0.708 | pathogenic | -1.751 | Destabilizing | 0.997 | D | 0.615 | neutral | D | 0.522697761 | None | None | N |
| L/G | 0.9957 | likely_pathogenic | 0.9958 | pathogenic | -3.578 | Highly Destabilizing | 0.999 | D | 0.887 | deleterious | None | None | None | None | N |
| L/H | 0.9959 | likely_pathogenic | 0.9963 | pathogenic | -3.267 | Highly Destabilizing | 1.0 | D | 0.902 | deleterious | None | None | None | None | N |
| L/I | 0.114 | likely_benign | 0.1456 | benign | -1.061 | Destabilizing | 0.923 | D | 0.567 | neutral | None | None | None | None | N |
| L/K | 0.9965 | likely_pathogenic | 0.9967 | pathogenic | -2.215 | Highly Destabilizing | 0.999 | D | 0.861 | deleterious | None | None | None | None | N |
| L/M | 0.3157 | likely_benign | 0.3501 | ambiguous | -1.234 | Destabilizing | 0.997 | D | 0.615 | neutral | N | 0.511848434 | None | None | N |
| L/N | 0.9984 | likely_pathogenic | 0.9986 | pathogenic | -2.984 | Highly Destabilizing | 0.999 | D | 0.921 | deleterious | None | None | None | None | N |
| L/P | 0.998 | likely_pathogenic | 0.9984 | pathogenic | -1.686 | Destabilizing | 0.999 | D | 0.915 | deleterious | None | None | None | None | N |
| L/Q | 0.9944 | likely_pathogenic | 0.9945 | pathogenic | -2.584 | Highly Destabilizing | 0.999 | D | 0.901 | deleterious | None | None | None | None | N |
| L/R | 0.9936 | likely_pathogenic | 0.9937 | pathogenic | -2.321 | Highly Destabilizing | 0.999 | D | 0.889 | deleterious | None | None | None | None | N |
| L/S | 0.9964 | likely_pathogenic | 0.9966 | pathogenic | -3.513 | Highly Destabilizing | 0.997 | D | 0.843 | deleterious | D | 0.550463254 | None | None | N |
| L/T | 0.9725 | likely_pathogenic | 0.9772 | pathogenic | -3.006 | Highly Destabilizing | 0.983 | D | 0.726 | prob.delet. | None | None | None | None | N |
| L/V | 0.1298 | likely_benign | 0.1615 | benign | -1.686 | Destabilizing | 0.198 | N | 0.293 | neutral | N | 0.469442422 | None | None | N |
| L/W | 0.9891 | likely_pathogenic | 0.9891 | pathogenic | -2.123 | Highly Destabilizing | 1.0 | D | 0.864 | deleterious | D | 0.550463254 | None | None | N |
| L/Y | 0.983 | likely_pathogenic | 0.9851 | pathogenic | -1.977 | Destabilizing | 0.999 | D | 0.732 | 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.