TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27353	82282;82283;82284	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
N2AB	25712	77359;77360;77361	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
N2A	24785	74578;74579;74580	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
N2B	18288	55087;55088;55089	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
Novex-1	18413	55462;55463;55464	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
Novex-2	18480	55663;55664;55665	chr2:178564075;178564074;178564073	chr2:179428802;179428801;179428800
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-140
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.2702
• 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/S	rs1704729039	None	0.999	N	0.547	0.604	0.316198179892	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9882	likely_pathogenic	0.9918	pathogenic	-0.571	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
N/C	0.9061	likely_pathogenic	0.9282	pathogenic	0.161	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
N/D	0.989	likely_pathogenic	0.9918	pathogenic	-0.888	Destabilizing	0.999	D	0.582	neutral	D	0.549461025	None	None	I
N/E	0.9984	likely_pathogenic	0.9988	pathogenic	-0.894	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
N/F	0.9986	likely_pathogenic	0.9987	pathogenic	-0.97	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
N/G	0.9796	likely_pathogenic	0.9831	pathogenic	-0.766	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	I
N/H	0.9587	likely_pathogenic	0.9644	pathogenic	-0.933	Destabilizing	1.0	D	0.765	deleterious	D	0.550728473	None	None	I
N/I	0.9864	likely_pathogenic	0.9907	pathogenic	-0.125	Destabilizing	1.0	D	0.743	deleterious	N	0.521356818	None	None	I
N/K	0.9982	likely_pathogenic	0.9986	pathogenic	-0.031	Destabilizing	1.0	D	0.72	prob.delet.	D	0.538700604	None	None	I
N/L	0.9709	likely_pathogenic	0.976	pathogenic	-0.125	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/M	0.989	likely_pathogenic	0.9912	pathogenic	0.598	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
N/P	0.9955	likely_pathogenic	0.9964	pathogenic	-0.248	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
N/Q	0.9974	likely_pathogenic	0.9978	pathogenic	-0.827	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
N/R	0.9958	likely_pathogenic	0.9966	pathogenic	0.115	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
N/S	0.636	likely_pathogenic	0.7033	pathogenic	-0.416	Destabilizing	0.999	D	0.547	neutral	N	0.503844766	None	None	I
N/T	0.9214	likely_pathogenic	0.9421	pathogenic	-0.283	Destabilizing	0.999	D	0.691	prob.neutral	D	0.538193625	None	None	I
N/V	0.9783	likely_pathogenic	0.9851	pathogenic	-0.248	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.875	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
N/Y	0.9904	likely_pathogenic	0.9914	pathogenic	-0.582	Destabilizing	1.0	D	0.767	deleterious	D	0.550728473	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.