Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22348 | 67267;67268;67269 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| N2AB | 20707 | 62344;62345;62346 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| N2A | 19780 | 59563;59564;59565 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| N2B | 13283 | 40072;40073;40074 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| Novex-1 | 13408 | 40447;40448;40449 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| Novex-2 | 13475 | 40648;40649;40650 | chr2:178580337;178580336;178580335 | chr2:179445064;179445063;179445062 |
| 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/A | None | None | 0.822 | N | 0.493 | 0.313 | 0.734690525238 | gnomAD-4.0.0 | 2.05386E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69939E-06 | 0 | 0 |
| V/I | rs776484491  |
-0.17 | 0.058 | N | 0.309 | 0.064 | 0.557090038421 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| V/I | rs776484491 |
-0.17 | 0.058 | N | 0.309 | 0.064 | 0.557090038421 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/I | rs776484491 |
-0.17 | 0.058 | N | 0.309 | 0.064 | 0.557090038421 | gnomAD-4.0.0 | 3.84758E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.18539E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2708 | likely_benign | 0.2822 | benign | -1.288 | Destabilizing | 0.822 | D | 0.493 | neutral | N | 0.510603972 | None | None | I |
| V/C | 0.8099 | likely_pathogenic | 0.8088 | pathogenic | -0.958 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | I |
| V/D | 0.6918 | likely_pathogenic | 0.7188 | pathogenic | -0.709 | Destabilizing | 0.89 | D | 0.747 | deleterious | N | 0.484553521 | None | None | I |
| V/E | 0.66 | likely_pathogenic | 0.6885 | pathogenic | -0.731 | Destabilizing | 0.956 | D | 0.714 | prob.delet. | None | None | None | None | I |
| V/F | 0.2976 | likely_benign | 0.302 | benign | -1.012 | Destabilizing | 0.032 | N | 0.349 | neutral | N | 0.484705278 | None | None | I |
| V/G | 0.4212 | ambiguous | 0.4598 | ambiguous | -1.577 | Destabilizing | 0.822 | D | 0.721 | prob.delet. | D | 0.522071759 | None | None | I |
| V/H | 0.7485 | likely_pathogenic | 0.7616 | pathogenic | -1.051 | Destabilizing | 0.994 | D | 0.753 | deleterious | None | None | None | None | I |
| V/I | 0.0862 | likely_benign | 0.082 | benign | -0.613 | Destabilizing | 0.058 | N | 0.309 | neutral | N | 0.463082171 | None | None | I |
| V/K | 0.7507 | likely_pathogenic | 0.781 | pathogenic | -0.983 | Destabilizing | 0.956 | D | 0.717 | prob.delet. | None | None | None | None | I |
| V/L | 0.2308 | likely_benign | 0.2208 | benign | -0.613 | Destabilizing | 0.489 | N | 0.472 | neutral | N | 0.454654689 | None | None | I |
| V/M | 0.2146 | likely_benign | 0.1883 | benign | -0.523 | Destabilizing | 0.978 | D | 0.572 | neutral | None | None | None | None | I |
| V/N | 0.3351 | likely_benign | 0.3621 | ambiguous | -0.743 | Destabilizing | 0.16 | N | 0.491 | neutral | None | None | None | None | I |
| V/P | 0.7976 | likely_pathogenic | 0.7989 | pathogenic | -0.802 | Destabilizing | 0.993 | D | 0.748 | deleterious | None | None | None | None | I |
| V/Q | 0.5765 | likely_pathogenic | 0.6026 | pathogenic | -0.921 | Destabilizing | 0.978 | D | 0.75 | deleterious | None | None | None | None | I |
| V/R | 0.6527 | likely_pathogenic | 0.7027 | pathogenic | -0.501 | Destabilizing | 0.978 | D | 0.767 | deleterious | None | None | None | None | I |
| V/S | 0.2744 | likely_benign | 0.3084 | benign | -1.32 | Destabilizing | 0.86 | D | 0.701 | prob.neutral | None | None | None | None | I |
| V/T | 0.2 | likely_benign | 0.2044 | benign | -1.228 | Destabilizing | 0.86 | D | 0.51 | neutral | None | None | None | None | I |
| V/W | 0.9186 | likely_pathogenic | 0.9105 | pathogenic | -1.127 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | I |
| V/Y | 0.6916 | likely_pathogenic | 0.7143 | pathogenic | -0.842 | Destabilizing | 0.915 | D | 0.708 | prob.delet. | 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.