Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14316 | 43171;43172;43173 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| N2AB | 12675 | 38248;38249;38250 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| N2A | 11748 | 35467;35468;35469 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| N2B | 5251 | 15976;15977;15978 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| Novex-1 | 5376 | 16351;16352;16353 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| Novex-2 | 5443 | 16552;16553;16554 | chr2:178633413;178633326;178633325 | chr2:179498140;179498053;179498052 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/S | None | None | 0.103 | D | 0.186 | 0.204 | 0.223146558224 | gnomAD-4.0.0 | 3.42206E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.49819E-06 | 0 | 0 |
| A/T | rs763386894  |
-0.617 | 0.811 | D | 0.25 | 0.246 | 0.313818047136 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.6E-05 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs763386894 |
-0.617 | 0.811 | D | 0.25 | 0.246 | 0.313818047136 | gnomAD-4.0.0 | 2.05323E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52551E-05 | None | 0 | 0 | 1.79928E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7782 | likely_pathogenic | 0.7709 | pathogenic | -0.875 | Destabilizing | 0.999 | D | 0.283 | neutral | None | None | None | None | N |
| A/D | 0.3566 | ambiguous | 0.2772 | benign | -0.722 | Destabilizing | 0.059 | N | 0.239 | neutral | D | 0.553233998 | None | None | N |
| A/E | 0.3043 | likely_benign | 0.2414 | benign | -0.851 | Destabilizing | 0.851 | D | 0.301 | neutral | None | None | None | None | N |
| A/F | 0.657 | likely_pathogenic | 0.5807 | pathogenic | -0.821 | Destabilizing | 0.996 | D | 0.409 | neutral | None | None | None | None | N |
| A/G | 0.1526 | likely_benign | 0.1408 | benign | -0.389 | Destabilizing | 0.811 | D | 0.251 | neutral | N | 0.493245942 | None | None | N |
| A/H | 0.6551 | likely_pathogenic | 0.6146 | pathogenic | -0.304 | Destabilizing | 0.999 | D | 0.422 | neutral | None | None | None | None | N |
| A/I | 0.6095 | likely_pathogenic | 0.5065 | ambiguous | -0.331 | Destabilizing | 0.988 | D | 0.289 | neutral | None | None | None | None | N |
| A/K | 0.5277 | ambiguous | 0.4544 | ambiguous | -0.83 | Destabilizing | 0.976 | D | 0.293 | neutral | None | None | None | None | N |
| A/L | 0.3646 | ambiguous | 0.3129 | benign | -0.331 | Destabilizing | 0.919 | D | 0.269 | neutral | None | None | None | None | N |
| A/M | 0.4562 | ambiguous | 0.3964 | ambiguous | -0.568 | Destabilizing | 0.999 | D | 0.334 | neutral | None | None | None | None | N |
| A/N | 0.3247 | likely_benign | 0.2716 | benign | -0.533 | Destabilizing | 0.976 | D | 0.376 | neutral | None | None | None | None | N |
| A/P | 0.1351 | likely_benign | 0.1294 | benign | -0.296 | Destabilizing | 0.059 | N | 0.201 | neutral | D | 0.603458927 | None | None | N |
| A/Q | 0.3971 | ambiguous | 0.3566 | ambiguous | -0.79 | Destabilizing | 0.988 | D | 0.275 | neutral | None | None | None | None | N |
| A/R | 0.51 | ambiguous | 0.4718 | ambiguous | -0.324 | Destabilizing | 0.976 | D | 0.281 | neutral | None | None | None | None | N |
| A/S | 0.1108 | likely_benign | 0.0971 | benign | -0.714 | Destabilizing | 0.103 | N | 0.186 | neutral | D | 0.523273289 | None | None | N |
| A/T | 0.1665 | likely_benign | 0.1297 | benign | -0.766 | Destabilizing | 0.811 | D | 0.25 | neutral | D | 0.567499973 | None | None | N |
| A/V | 0.3009 | likely_benign | 0.2418 | benign | -0.296 | Destabilizing | 0.896 | D | 0.226 | neutral | N | 0.463176038 | None | None | N |
| A/W | 0.8986 | likely_pathogenic | 0.8833 | pathogenic | -0.971 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| A/Y | 0.7004 | likely_pathogenic | 0.6588 | pathogenic | -0.639 | Destabilizing | 0.996 | D | 0.411 | 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.