Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18240 | 54943;54944;54945 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| N2AB | 16599 | 50020;50021;50022 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| N2A | 15672 | 47239;47240;47241 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| N2B | 9175 | 27748;27749;27750 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| Novex-1 | 9300 | 28123;28124;28125 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| Novex-2 | 9367 | 28324;28325;28326 | chr2:178603969;178603968;178603967 | chr2:179468696;179468695;179468694 |
| 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 | rs375141729  |
-0.304 | 0.213 | N | 0.293 | 0.111 | None | gnomAD-2.1.1 | 4.64E-05 | None | None | None | None | N | None | 4.13873E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.35E-05 | 0 |
| V/I | rs375141729 |
-0.304 | 0.213 | N | 0.293 | 0.111 | None | gnomAD-3.1.2 | 1.84327E-04 | None | None | None | None | N | None | 5.3135E-04 | 1.3132E-04 | 0 | 0 | 0 | None | 0 | 9.49367E-03 | 1.47E-05 | 0 | 0 |
| V/I | rs375141729 |
-0.304 | 0.213 | N | 0.293 | 0.111 | None | gnomAD-4.0.0 | 5.20872E-05 | None | None | None | None | N | None | 6.00528E-04 | 5.00417E-05 | None | 0 | 0 | None | 0 | 4.96032E-04 | 1.86584E-05 | 1.0988E-05 | 1.60195E-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 | 0.2063 | likely_benign | 0.1599 | benign | -1.33 | Destabilizing | 0.863 | D | 0.43 | neutral | N | 0.439730017 | None | None | N |
| V/C | 0.537 | ambiguous | 0.5208 | ambiguous | -0.862 | Destabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| V/D | 0.5051 | ambiguous | 0.4357 | ambiguous | -1.154 | Destabilizing | 0.991 | D | 0.661 | neutral | N | 0.503242777 | None | None | N |
| V/E | 0.3522 | ambiguous | 0.2938 | benign | -1.062 | Destabilizing | 0.993 | D | 0.611 | neutral | None | None | None | None | N |
| V/F | 0.1603 | likely_benign | 0.1442 | benign | -0.801 | Destabilizing | 0.993 | D | 0.587 | neutral | N | 0.51624936 | None | None | N |
| V/G | 0.2108 | likely_benign | 0.1717 | benign | -1.726 | Destabilizing | 0.991 | D | 0.653 | neutral | N | 0.470554356 | None | None | N |
| V/H | 0.4896 | ambiguous | 0.4355 | ambiguous | -1.216 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| V/I | 0.0856 | likely_benign | 0.0772 | benign | -0.313 | Destabilizing | 0.213 | N | 0.293 | neutral | N | 0.48627317 | None | None | N |
| V/K | 0.3162 | likely_benign | 0.2732 | benign | -1.113 | Destabilizing | 0.993 | D | 0.612 | neutral | None | None | None | None | N |
| V/L | 0.2184 | likely_benign | 0.1753 | benign | -0.313 | Destabilizing | 0.889 | D | 0.401 | neutral | N | 0.471285075 | None | None | N |
| V/M | 0.1463 | likely_benign | 0.121 | benign | -0.292 | Destabilizing | 0.986 | D | 0.55 | neutral | None | None | None | None | N |
| V/N | 0.2593 | likely_benign | 0.2169 | benign | -1.151 | Destabilizing | 0.993 | D | 0.663 | neutral | None | None | None | None | N |
| V/P | 0.9021 | likely_pathogenic | 0.8793 | pathogenic | -0.618 | Destabilizing | 0.998 | D | 0.608 | neutral | None | None | None | None | N |
| V/Q | 0.2555 | likely_benign | 0.217 | benign | -1.16 | Destabilizing | 0.998 | D | 0.609 | neutral | None | None | None | None | N |
| V/R | 0.2783 | likely_benign | 0.242 | benign | -0.754 | Destabilizing | 0.993 | D | 0.663 | neutral | None | None | None | None | N |
| V/S | 0.2173 | likely_benign | 0.174 | benign | -1.734 | Destabilizing | 0.973 | D | 0.581 | neutral | None | None | None | None | N |
| V/T | 0.1719 | likely_benign | 0.1445 | benign | -1.513 | Destabilizing | 0.214 | N | 0.337 | neutral | None | None | None | None | N |
| V/W | 0.7995 | likely_pathogenic | 0.7322 | pathogenic | -1.124 | Destabilizing | 0.999 | D | 0.575 | neutral | None | None | None | None | N |
| V/Y | 0.491 | ambiguous | 0.453 | ambiguous | -0.741 | Destabilizing | 0.998 | D | 0.577 | neutral | 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.