Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20066 | 60421;60422;60423 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| N2AB | 18425 | 55498;55499;55500 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| N2A | 17498 | 52717;52718;52719 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| N2B | 11001 | 33226;33227;33228 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| Novex-1 | 11126 | 33601;33602;33603 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| Novex-2 | 11193 | 33802;33803;33804 | chr2:178591623;178591622;178591621 | chr2:179456350;179456349;179456348 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs750217838  |
-0.537 | 1.0 | N | 0.867 | 0.467 | None | gnomAD-2.1.1 | 7.52E-05 | None | None | None | None | N | None | 4.14E-05 | 2.83994E-04 | None | 0 | 0 | None | 3.3E-05 | None | 0 | 7.05E-05 | 0 |
| P/L | rs750217838 |
-0.537 | 1.0 | N | 0.867 | 0.467 | None | gnomAD-3.1.2 | 1.11816E-04 | None | None | None | None | N | None | 7.24E-05 | 3.93236E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.02968E-04 | 0 | 4.78927E-04 |
| P/L | rs750217838 |
-0.537 | 1.0 | N | 0.867 | 0.467 | None | gnomAD-4.0.0 | 4.4029E-05 | None | None | None | None | N | None | 4.00952E-05 | 2.50476E-04 | None | 0 | 2.23105E-05 | None | 0 | 3.29598E-04 | 3.56111E-05 | 2.20609E-05 | 9.61138E-05 |
| P/S | None | None | 1.0 | N | 0.839 | 0.341 | 0.51748813702 | gnomAD-4.0.0 | 2.73766E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59863E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.1637 | likely_benign | 0.1523 | benign | -1.126 | Destabilizing | 0.999 | D | 0.822 | deleterious | N | 0.48558697 | None | None | N |
| P/C | 0.849 | likely_pathogenic | 0.8551 | pathogenic | -0.796 | Destabilizing | 1.0 | D | 0.864 | deleterious | None | None | None | None | N |
| P/D | 0.8037 | likely_pathogenic | 0.789 | pathogenic | -0.987 | Destabilizing | 1.0 | D | 0.851 | deleterious | None | None | None | None | N |
| P/E | 0.656 | likely_pathogenic | 0.6489 | pathogenic | -1.049 | Destabilizing | 1.0 | D | 0.842 | deleterious | None | None | None | None | N |
| P/F | 0.8494 | likely_pathogenic | 0.8176 | pathogenic | -0.991 | Destabilizing | 1.0 | D | 0.901 | deleterious | None | None | None | None | N |
| P/G | 0.6252 | likely_pathogenic | 0.618 | pathogenic | -1.36 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | N |
| P/H | 0.5867 | likely_pathogenic | 0.5538 | ambiguous | -0.823 | Destabilizing | 1.0 | D | 0.868 | deleterious | None | None | None | None | N |
| P/I | 0.6851 | likely_pathogenic | 0.6535 | pathogenic | -0.617 | Destabilizing | 1.0 | D | 0.909 | deleterious | None | None | None | None | N |
| P/K | 0.71 | likely_pathogenic | 0.6976 | pathogenic | -1.039 | Destabilizing | 1.0 | D | 0.844 | deleterious | None | None | None | None | N |
| P/L | 0.3338 | likely_benign | 0.2931 | benign | -0.617 | Destabilizing | 1.0 | D | 0.867 | deleterious | N | 0.514873401 | None | None | N |
| P/M | 0.6795 | likely_pathogenic | 0.6622 | pathogenic | -0.485 | Destabilizing | 1.0 | D | 0.867 | deleterious | None | None | None | None | N |
| P/N | 0.7257 | likely_pathogenic | 0.7129 | pathogenic | -0.776 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| P/Q | 0.5039 | ambiguous | 0.4744 | ambiguous | -1.017 | Destabilizing | 1.0 | D | 0.879 | deleterious | D | 0.52664778 | None | None | N |
| P/R | 0.5562 | ambiguous | 0.5183 | ambiguous | -0.411 | Destabilizing | 1.0 | D | 0.911 | deleterious | N | 0.51538038 | None | None | N |
| P/S | 0.3211 | likely_benign | 0.3021 | benign | -1.195 | Destabilizing | 1.0 | D | 0.839 | deleterious | N | 0.48541284 | None | None | N |
| P/T | 0.3041 | likely_benign | 0.2858 | benign | -1.158 | Destabilizing | 1.0 | D | 0.835 | deleterious | N | 0.484612692 | None | None | N |
| P/V | 0.495 | ambiguous | 0.472 | ambiguous | -0.751 | Destabilizing | 1.0 | D | 0.871 | deleterious | None | None | None | None | N |
| P/W | 0.9291 | likely_pathogenic | 0.915 | pathogenic | -1.102 | Destabilizing | 1.0 | D | 0.847 | deleterious | None | None | None | None | N |
| P/Y | 0.8503 | likely_pathogenic | 0.8266 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.909 | 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.