Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30578 | 91957;91958;91959 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| N2AB | 28937 | 87034;87035;87036 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| N2A | 28010 | 84253;84254;84255 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| N2B | 21513 | 64762;64763;64764 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| Novex-1 | 21638 | 65137;65138;65139 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| Novex-2 | 21705 | 65338;65339;65340 | chr2:178550106;178550105;178550104 | chr2:179414833;179414832;179414831 |
| 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/I | rs727504672  |
0.16 | 0.958 | N | 0.218 | 0.242 | None | gnomAD-2.1.1 | 9.27E-05 | None | None | None | None | I | None | 4.13E-05 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 1.87283E-04 | 0 |
| V/I | rs727504672 |
0.16 | 0.958 | N | 0.218 | 0.242 | None | gnomAD-3.1.2 | 1.24875E-04 | None | None | None | None | I | None | 7.24E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 1.58228E-02 | 1.32306E-04 | 0 | 4.77555E-04 |
| V/I | rs727504672 |
0.16 | 0.958 | N | 0.218 | 0.242 | None | gnomAD-4.0.0 | 9.4806E-05 | None | None | None | None | I | None | 6.66542E-05 | 1.6665E-05 | None | 0 | 4.45752E-05 | None | 3.12422E-05 | 8.25083E-04 | 1.05104E-04 | 3.29381E-05 | 1.76039E-04 |
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 | 0.1911 | likely_benign | 0.1891 | benign | -0.264 | Destabilizing | 0.005 | N | 0.147 | neutral | N | 0.47781955 | None | None | I |
| V/C | 0.6861 | likely_pathogenic | 0.6816 | pathogenic | -0.653 | Destabilizing | 0.993 | D | 0.249 | neutral | None | None | None | None | I |
| V/D | 0.3814 | ambiguous | 0.3683 | ambiguous | -0.021 | Destabilizing | 0.016 | N | 0.279 | neutral | None | None | None | None | I |
| V/E | 0.3373 | likely_benign | 0.3231 | benign | -0.143 | Destabilizing | 0.669 | D | 0.286 | neutral | N | 0.439645164 | None | None | I |
| V/F | 0.174 | likely_benign | 0.1719 | benign | -0.646 | Destabilizing | 0.974 | D | 0.25 | neutral | None | None | None | None | I |
| V/G | 0.23 | likely_benign | 0.2322 | benign | -0.338 | Destabilizing | 0.002 | N | 0.192 | neutral | N | 0.460908657 | None | None | I |
| V/H | 0.529 | ambiguous | 0.5335 | ambiguous | -0.035 | Destabilizing | 0.998 | D | 0.353 | neutral | None | None | None | None | I |
| V/I | 0.0725 | likely_benign | 0.0731 | benign | -0.225 | Destabilizing | 0.958 | D | 0.218 | neutral | N | 0.471587011 | None | None | I |
| V/K | 0.4179 | ambiguous | 0.4011 | ambiguous | -0.177 | Destabilizing | 0.842 | D | 0.309 | neutral | None | None | None | None | I |
| V/L | 0.2031 | likely_benign | 0.1949 | benign | -0.225 | Destabilizing | 0.809 | D | 0.227 | neutral | N | 0.456694916 | None | None | I |
| V/M | 0.1351 | likely_benign | 0.1365 | benign | -0.312 | Destabilizing | 0.991 | D | 0.227 | neutral | None | None | None | None | I |
| V/N | 0.2158 | likely_benign | 0.2165 | benign | 0.01 | Stabilizing | 0.842 | D | 0.365 | neutral | None | None | None | None | I |
| V/P | 0.8594 | likely_pathogenic | 0.8451 | pathogenic | -0.207 | Destabilizing | 0.974 | D | 0.333 | neutral | None | None | None | None | I |
| V/Q | 0.3424 | ambiguous | 0.3413 | ambiguous | -0.205 | Destabilizing | 0.974 | D | 0.323 | neutral | None | None | None | None | I |
| V/R | 0.4112 | ambiguous | 0.4003 | ambiguous | 0.234 | Stabilizing | 0.974 | D | 0.369 | neutral | None | None | None | None | I |
| V/S | 0.1983 | likely_benign | 0.2002 | benign | -0.333 | Destabilizing | 0.728 | D | 0.26 | neutral | None | None | None | None | I |
| V/T | 0.1612 | likely_benign | 0.1622 | benign | -0.356 | Destabilizing | 0.842 | D | 0.15 | neutral | None | None | None | None | I |
| V/W | 0.8271 | likely_pathogenic | 0.834 | pathogenic | -0.719 | Destabilizing | 0.998 | D | 0.392 | neutral | None | None | None | None | I |
| V/Y | 0.5091 | ambiguous | 0.5117 | ambiguous | -0.407 | Destabilizing | 0.991 | D | 0.244 | neutral | None | None | 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.