TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9666	29221;29222;29223	chr2:178707571;178707570;178707569	chr2:179572298;179572297;179572296
N2AB	9349	28270;28271;28272	chr2:178707571;178707570;178707569	chr2:179572298;179572297;179572296
N2A	8422	25489;25490;25491	chr2:178707571;178707570;178707569	chr2:179572298;179572297;179572296
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-82
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1802
• Predicted PPI site: I

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
N/K	None	None	1.0	None	0.723	0.463	0.132336055621	gnomAD-4.0.0	1.5914E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43312E-05	0
N/S	None	None	0.999	None	0.58	0.417	0.185906805712	gnomAD-4.0.0	3.18275E-06	None	None	None	None	I	None	0	0	None	4.76872E-05	0	None	0	0	2.85834E-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
N/A	0.9864	likely_pathogenic	0.9529	pathogenic	-0.808	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/C	0.9496	likely_pathogenic	0.8832	pathogenic	-0.103	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
N/D	0.97	likely_pathogenic	0.9149	pathogenic	-0.986	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
N/E	0.9982	likely_pathogenic	0.9953	pathogenic	-0.953	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
N/F	0.9987	likely_pathogenic	0.9953	pathogenic	-0.98	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
N/G	0.9667	likely_pathogenic	0.8995	pathogenic	-1.053	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	I
N/H	0.9578	likely_pathogenic	0.8808	pathogenic	-1.016	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/I	0.9915	likely_pathogenic	0.9723	pathogenic	-0.218	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
N/K	0.9982	likely_pathogenic	0.9934	pathogenic	-0.17	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
N/L	0.9767	likely_pathogenic	0.9327	pathogenic	-0.218	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
N/M	0.9922	likely_pathogenic	0.9735	pathogenic	0.416	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
N/P	0.9959	likely_pathogenic	0.9861	pathogenic	-0.388	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/Q	0.9975	likely_pathogenic	0.9918	pathogenic	-0.997	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
N/R	0.9963	likely_pathogenic	0.9882	pathogenic	-0.032	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/S	0.5241	ambiguous	0.3388	benign	-0.696	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
N/T	0.8926	likely_pathogenic	0.765	pathogenic	-0.505	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
N/V	0.9843	likely_pathogenic	0.9494	pathogenic	-0.388	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/W	0.9996	likely_pathogenic	0.9986	pathogenic	-0.783	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
N/Y	0.9894	likely_pathogenic	0.9639	pathogenic	-0.527	Destabilizing	1.0	D	0.727	prob.delet.	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.