Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26128 | 78607;78608;78609 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| N2AB | 24487 | 73684;73685;73686 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| N2A | 23560 | 70903;70904;70905 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| N2B | 17063 | 51412;51413;51414 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| Novex-1 | 17188 | 51787;51788;51789 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| Novex-2 | 17255 | 51988;51989;51990 | chr2:178567750;178567749;178567748 | chr2:179432477;179432476;179432475 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs373530641  |
-1.557 | 1.0 | N | 0.758 | 0.42 | None | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.68E-05 | 0 |
| R/C | rs373530641 |
-1.557 | 1.0 | N | 0.758 | 0.42 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/C | rs373530641 |
-1.557 | 1.0 | N | 0.758 | 0.42 | None | gnomAD-4.0.0 | 2.48008E-05 | None | None | None | None | N | None | 2.6713E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.71363E-05 | 1.09825E-05 | 8.01025E-05 |
| R/H | rs757957389 |
-2.097 | 0.999 | N | 0.613 | 0.266 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 8.27E-05 | 0 | None | 0 | 5.15E-05 | None | 0 | None | 0 | 7.84E-06 | 0 |
| R/H | rs757957389 |
-2.097 | 0.999 | N | 0.613 | 0.266 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.65E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs757957389 |
-2.097 | 0.999 | N | 0.613 | 0.266 | None | gnomAD-4.0.0 | 9.30003E-06 | None | None | None | None | N | None | 6.67735E-05 | 1.66856E-05 | None | 0 | 2.23174E-05 | None | 0 | 0 | 5.93605E-06 | 0 | 1.60195E-05 |
| R/L | None | None | 0.975 | N | 0.681 | 0.46 | 0.524533156562 | gnomAD-4.0.0 | 6.84556E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15977E-05 | 0 |
| R/P | rs757957389 |
-1.229 | 0.996 | N | 0.797 | 0.492 | 0.450248222533 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.11769E-04 | None | 0 | None | 0 | 0 | 0 |
| R/S | None | None | 0.975 | N | 0.643 | 0.388 | 0.358340041657 | gnomAD-4.0.0 | 1.36911E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79976E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8723 | likely_pathogenic | 0.8618 | pathogenic | -2.046 | Highly Destabilizing | 0.953 | D | 0.555 | neutral | None | None | None | None | N |
| R/C | 0.3537 | ambiguous | 0.3076 | benign | -1.998 | Destabilizing | 1.0 | D | 0.758 | deleterious | N | 0.480260009 | None | None | N |
| R/D | 0.987 | likely_pathogenic | 0.9874 | pathogenic | -0.791 | Destabilizing | 0.986 | D | 0.783 | deleterious | None | None | None | None | N |
| R/E | 0.8668 | likely_pathogenic | 0.8545 | pathogenic | -0.602 | Destabilizing | 0.91 | D | 0.467 | neutral | None | None | None | None | N |
| R/F | 0.9481 | likely_pathogenic | 0.9439 | pathogenic | -1.461 | Destabilizing | 0.998 | D | 0.795 | deleterious | None | None | None | None | N |
| R/G | 0.8264 | likely_pathogenic | 0.8261 | pathogenic | -2.373 | Highly Destabilizing | 0.975 | D | 0.681 | prob.neutral | N | 0.499098279 | None | None | N |
| R/H | 0.3482 | ambiguous | 0.3358 | benign | -2.224 | Highly Destabilizing | 0.999 | D | 0.613 | neutral | N | 0.505530287 | None | None | N |
| R/I | 0.8473 | likely_pathogenic | 0.8066 | pathogenic | -1.108 | Destabilizing | 0.993 | D | 0.807 | deleterious | None | None | None | None | N |
| R/K | 0.1164 | likely_benign | 0.1181 | benign | -1.547 | Destabilizing | 0.06 | N | 0.181 | neutral | None | None | None | None | N |
| R/L | 0.6874 | likely_pathogenic | 0.64 | pathogenic | -1.108 | Destabilizing | 0.975 | D | 0.681 | prob.neutral | N | 0.501958662 | None | None | N |
| R/M | 0.6589 | likely_pathogenic | 0.6196 | pathogenic | -1.514 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| R/N | 0.9496 | likely_pathogenic | 0.9488 | pathogenic | -1.242 | Destabilizing | 0.986 | D | 0.587 | neutral | None | None | None | None | N |
| R/P | 0.9977 | likely_pathogenic | 0.9975 | pathogenic | -1.408 | Destabilizing | 0.996 | D | 0.797 | deleterious | N | 0.514493509 | None | None | N |
| R/Q | 0.2456 | likely_benign | 0.2206 | benign | -1.277 | Destabilizing | 0.986 | D | 0.567 | neutral | None | None | None | None | N |
| R/S | 0.9456 | likely_pathogenic | 0.9431 | pathogenic | -2.248 | Highly Destabilizing | 0.975 | D | 0.643 | neutral | N | 0.482395922 | None | None | N |
| R/T | 0.8684 | likely_pathogenic | 0.855 | pathogenic | -1.856 | Destabilizing | 0.986 | D | 0.733 | prob.delet. | None | None | None | None | N |
| R/V | 0.8773 | likely_pathogenic | 0.852 | pathogenic | -1.408 | Destabilizing | 0.993 | D | 0.797 | deleterious | None | None | None | None | N |
| R/W | 0.7278 | likely_pathogenic | 0.6834 | pathogenic | -0.905 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | None | None | None | None | N |
| R/Y | 0.8587 | likely_pathogenic | 0.846 | pathogenic | -0.753 | Destabilizing | 0.998 | D | 0.8 | 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.