Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19978 | 60157;60158;60159 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| N2AB | 18337 | 55234;55235;55236 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| N2A | 17410 | 52453;52454;52455 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| N2B | 10913 | 32962;32963;32964 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| Novex-1 | 11038 | 33337;33338;33339 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| Novex-2 | 11105 | 33538;33539;33540 | chr2:178591887;178591886;178591885 | chr2:179456614;179456613;179456612 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | rs1366471902  |
-2.178 | 0.999 | D | 0.813 | 0.479 | 0.546131560702 | gnomAD-2.1.1 | 8.26E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.81E-05 | 0 |
| P/A | rs1366471902 |
-2.178 | 0.999 | D | 0.813 | 0.479 | 0.546131560702 | gnomAD-4.0.0 | 3.21447E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.74303E-06 | 0 | 0 |
| P/L | rs1303172310 |
-0.908 | 1.0 | D | 0.855 | 0.477 | 0.772265227283 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 0 |
| P/L | rs1303172310 |
-0.908 | 1.0 | D | 0.855 | 0.477 | 0.772265227283 | gnomAD-4.0.0 | 4.81012E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.3055E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.6156 | likely_pathogenic | 0.7104 | pathogenic | -1.821 | Destabilizing | 0.999 | D | 0.813 | deleterious | D | 0.525817497 | None | None | N |
| P/C | 0.9513 | likely_pathogenic | 0.9727 | pathogenic | -2.018 | Highly Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | N |
| P/D | 0.999 | likely_pathogenic | 0.9992 | pathogenic | -3.307 | Highly Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/E | 0.9969 | likely_pathogenic | 0.9977 | pathogenic | -3.213 | Highly Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| P/F | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -1.153 | Destabilizing | 1.0 | D | 0.873 | deleterious | None | None | None | None | N |
| P/G | 0.9848 | likely_pathogenic | 0.9881 | pathogenic | -2.185 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| P/H | 0.996 | likely_pathogenic | 0.9972 | pathogenic | -1.668 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| P/I | 0.9799 | likely_pathogenic | 0.9876 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.812 | deleterious | None | None | None | None | N |
| P/K | 0.9976 | likely_pathogenic | 0.9983 | pathogenic | -1.657 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| P/L | 0.9536 | likely_pathogenic | 0.9674 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.855 | deleterious | D | 0.540287674 | None | None | N |
| P/M | 0.9915 | likely_pathogenic | 0.9943 | pathogenic | -1.1 | Destabilizing | 1.0 | D | 0.821 | deleterious | None | None | None | None | N |
| P/N | 0.9983 | likely_pathogenic | 0.9988 | pathogenic | -1.946 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| P/Q | 0.9931 | likely_pathogenic | 0.995 | pathogenic | -2.029 | Highly Destabilizing | 1.0 | D | 0.861 | deleterious | D | 0.553329501 | None | None | N |
| P/R | 0.9904 | likely_pathogenic | 0.9931 | pathogenic | -1.241 | Destabilizing | 1.0 | D | 0.851 | deleterious | D | 0.552822522 | None | None | N |
| P/S | 0.9481 | likely_pathogenic | 0.9643 | pathogenic | -2.32 | Highly Destabilizing | 1.0 | D | 0.795 | deleterious | D | 0.552062053 | None | None | N |
| P/T | 0.9391 | likely_pathogenic | 0.9607 | pathogenic | -2.121 | Highly Destabilizing | 1.0 | D | 0.807 | deleterious | N | 0.505257707 | None | None | N |
| P/V | 0.9184 | likely_pathogenic | 0.9502 | pathogenic | -1.149 | Destabilizing | 1.0 | D | 0.859 | deleterious | None | None | None | None | N |
| P/W | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -1.539 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/Y | 0.9992 | likely_pathogenic | 0.9995 | pathogenic | -1.242 | Destabilizing | 1.0 | D | 0.883 | 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.