Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31571 | 94936;94937;94938 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| N2AB | 29930 | 90013;90014;90015 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| N2A | 29003 | 87232;87233;87234 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| N2B | 22506 | 67741;67742;67743 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| Novex-1 | 22631 | 68116;68117;68118 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| Novex-2 | 22698 | 68317;68318;68319 | chr2:178546717;178546716;178546715 | chr2:179411444;179411443;179411442 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs140081451  |
-0.255 | 0.989 | D | 0.719 | 0.418 | 0.57803241275 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| V/M | rs140081451 |
-0.255 | 0.989 | D | 0.719 | 0.418 | 0.57803241275 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.92678E-04 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/M | rs140081451 |
-0.255 | 0.989 | D | 0.719 | 0.418 | 0.57803241275 | gnomAD-4.0.0 | 2.04487E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22856E-05 | None | 0 | 0 | 2.71241E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.7446 | likely_pathogenic | 0.6183 | pathogenic | -1.777 | Destabilizing | 0.822 | D | 0.654 | neutral | N | 0.479809618 | None | None | N |
| V/C | 0.9677 | likely_pathogenic | 0.9523 | pathogenic | -1.505 | Destabilizing | 0.998 | D | 0.832 | deleterious | None | None | None | None | N |
| V/D | 0.9992 | likely_pathogenic | 0.9974 | pathogenic | -1.944 | Destabilizing | 0.993 | D | 0.871 | deleterious | None | None | None | None | N |
| V/E | 0.9961 | likely_pathogenic | 0.9904 | pathogenic | -1.693 | Destabilizing | 0.99 | D | 0.877 | deleterious | D | 0.546568325 | None | None | N |
| V/F | 0.969 | likely_pathogenic | 0.931 | pathogenic | -1.015 | Destabilizing | 0.956 | D | 0.823 | deleterious | None | None | None | None | N |
| V/G | 0.9754 | likely_pathogenic | 0.9536 | pathogenic | -2.352 | Highly Destabilizing | 0.971 | D | 0.88 | deleterious | D | 0.55792463 | None | None | N |
| V/H | 0.9992 | likely_pathogenic | 0.998 | pathogenic | -2.142 | Highly Destabilizing | 0.998 | D | 0.879 | deleterious | None | None | None | None | N |
| V/I | 0.1475 | likely_benign | 0.105 | benign | -0.17 | Destabilizing | 0.019 | N | 0.198 | neutral | None | None | None | None | N |
| V/K | 0.9983 | likely_pathogenic | 0.9959 | pathogenic | -1.433 | Destabilizing | 0.978 | D | 0.881 | deleterious | None | None | None | None | N |
| V/L | 0.8378 | likely_pathogenic | 0.7207 | pathogenic | -0.17 | Destabilizing | 0.455 | N | 0.551 | neutral | N | 0.474442977 | None | None | N |
| V/M | 0.842 | likely_pathogenic | 0.7131 | pathogenic | -0.367 | Destabilizing | 0.989 | D | 0.719 | prob.delet. | D | 0.523184151 | None | None | N |
| V/N | 0.9965 | likely_pathogenic | 0.989 | pathogenic | -1.808 | Destabilizing | 0.993 | D | 0.902 | deleterious | None | None | None | None | N |
| V/P | 0.9964 | likely_pathogenic | 0.9896 | pathogenic | -0.677 | Destabilizing | 0.993 | D | 0.872 | deleterious | None | None | None | None | N |
| V/Q | 0.9956 | likely_pathogenic | 0.9897 | pathogenic | -1.546 | Destabilizing | 0.993 | D | 0.906 | deleterious | None | None | None | None | N |
| V/R | 0.9963 | likely_pathogenic | 0.9923 | pathogenic | -1.491 | Destabilizing | 0.993 | D | 0.908 | deleterious | None | None | None | None | N |
| V/S | 0.9737 | likely_pathogenic | 0.9426 | pathogenic | -2.511 | Highly Destabilizing | 0.978 | D | 0.879 | deleterious | None | None | None | None | N |
| V/T | 0.9278 | likely_pathogenic | 0.8764 | pathogenic | -2.083 | Highly Destabilizing | 0.86 | D | 0.716 | prob.delet. | None | None | None | None | N |
| V/W | 0.9998 | likely_pathogenic | 0.9995 | pathogenic | -1.466 | Destabilizing | 0.998 | D | 0.851 | deleterious | None | None | None | None | N |
| V/Y | 0.9978 | likely_pathogenic | 0.9947 | pathogenic | -1.044 | Destabilizing | 0.978 | D | 0.815 | deleterious | 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.