Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4780 | 14563;14564;14565 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| N2AB | 4463 | 13612;13613;13614 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| N2A | 3536 | 10831;10832;10833 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| N2B | 4417 | 13474;13475;13476 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| Novex-1 | 4542 | 13849;13850;13851 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| Novex-2 | 4609 | 14050;14051;14052 | chr2:178738115;178738114;178738113 | chr2:179602842;179602841;179602840 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs147879266  |
0.027 | 0.979 | N | 0.452 | 0.207 | None | gnomAD-2.1.1 | 8.93E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.02627E-03 | None | 1.30787E-04 | None | 0 | 7.82E-06 | 0 |
| S/N | rs147879266 |
0.027 | 0.979 | N | 0.452 | 0.207 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 7.70713E-04 | None | 0 | 0 | 1.47E-05 | 6.21633E-04 | 0 |
| S/N | rs147879266 |
0.027 | 0.979 | N | 0.452 | 0.207 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| S/N | rs147879266 |
0.027 | 0.979 | N | 0.452 | 0.207 | None |
Itoh-Satoh (2002)
| None |
DCM 
|
het | None | None | I | Genetic analysis of JP DCM families | None | None | None | None | None | None | None | None | None | None | None |
| S/N | rs147879266 |
0.027 | 0.979 | N | 0.452 | 0.207 | None | gnomAD-4.0.0 | 4.39978E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.04794E-03 | None | 0 | 0 | 3.39068E-06 | 1.64712E-04 | 8.00333E-05 |
| S/R | rs1574048697 |
None | 0.994 | N | 0.502 | 0.365 | 0.547851268036 | gnomAD-4.0.0 | 1.59164E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77454E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1265 | likely_benign | 0.1458 | benign | -0.412 | Destabilizing | 0.927 | D | 0.404 | neutral | None | None | None | None | I |
| S/C | 0.2504 | likely_benign | 0.2984 | benign | -0.308 | Destabilizing | 0.999 | D | 0.501 | neutral | D | 0.619047235 | None | None | I |
| S/D | 0.6042 | likely_pathogenic | 0.7131 | pathogenic | 0.075 | Stabilizing | 0.984 | D | 0.413 | neutral | None | None | None | None | I |
| S/E | 0.641 | likely_pathogenic | 0.7449 | pathogenic | -0.03 | Destabilizing | 0.984 | D | 0.416 | neutral | None | None | None | None | I |
| S/F | 0.2871 | likely_benign | 0.3671 | ambiguous | -1.032 | Destabilizing | 0.183 | N | 0.427 | neutral | None | None | None | None | I |
| S/G | 0.2119 | likely_benign | 0.2652 | benign | -0.503 | Destabilizing | 0.979 | D | 0.365 | neutral | D | 0.581882658 | None | None | I |
| S/H | 0.5875 | likely_pathogenic | 0.6474 | pathogenic | -0.993 | Destabilizing | 1.0 | D | 0.494 | neutral | None | None | None | None | I |
| S/I | 0.3161 | likely_benign | 0.4108 | ambiguous | -0.303 | Destabilizing | 0.921 | D | 0.546 | neutral | N | 0.509717754 | None | None | I |
| S/K | 0.8805 | likely_pathogenic | 0.921 | pathogenic | -0.479 | Destabilizing | 0.984 | D | 0.411 | neutral | None | None | None | None | I |
| S/L | 0.1772 | likely_benign | 0.2262 | benign | -0.303 | Destabilizing | 0.939 | D | 0.502 | neutral | None | None | None | None | I |
| S/M | 0.2975 | likely_benign | 0.3537 | ambiguous | -0.002 | Destabilizing | 0.995 | D | 0.501 | neutral | None | None | None | None | I |
| S/N | 0.258 | likely_benign | 0.323 | benign | -0.178 | Destabilizing | 0.979 | D | 0.452 | neutral | N | 0.506307175 | None | None | I |
| S/P | 0.8959 | likely_pathogenic | 0.9317 | pathogenic | -0.312 | Destabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | I |
| S/Q | 0.7132 | likely_pathogenic | 0.7631 | pathogenic | -0.477 | Destabilizing | 0.999 | D | 0.471 | neutral | None | None | None | None | I |
| S/R | 0.8306 | likely_pathogenic | 0.8868 | pathogenic | -0.235 | Destabilizing | 0.994 | D | 0.502 | neutral | N | 0.505451618 | None | None | I |
| S/T | 0.1117 | likely_benign | 0.129 | benign | -0.316 | Destabilizing | 0.238 | N | 0.229 | neutral | N | 0.512688766 | None | None | I |
| S/V | 0.2946 | likely_benign | 0.3762 | ambiguous | -0.312 | Destabilizing | 0.293 | N | 0.403 | neutral | None | None | None | None | I |
| S/W | 0.5456 | ambiguous | 0.6185 | pathogenic | -1.014 | Destabilizing | 1.0 | D | 0.611 | neutral | None | None | None | None | I |
| S/Y | 0.308 | likely_benign | 0.3771 | ambiguous | -0.745 | Destabilizing | 0.982 | D | 0.589 | 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.