TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8487	25684;25685;25686	chr2:178717275;178717274;178717273	chr2:179582002;179582001;179582000
N2AB	8170	24733;24734;24735	chr2:178717275;178717274;178717273	chr2:179582002;179582001;179582000
N2A	7243	21952;21953;21954	chr2:178717275;178717274;178717273	chr2:179582002;179582001;179582000
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-70
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2467
• Predicted PPI site: N

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
I/V	rs1368912492	None	None	N	0.255	0.22	0.366085729538	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
I/A	0.877	likely_pathogenic	0.826	pathogenic	-1.797	Destabilizing	0.851	D	0.705	prob.neutral	None	None	None	None	N
I/C	0.9316	likely_pathogenic	0.9049	pathogenic	-1.043	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
I/D	0.9928	likely_pathogenic	0.9905	pathogenic	-1.38	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
I/E	0.9824	likely_pathogenic	0.9781	pathogenic	-1.317	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
I/F	0.3876	ambiguous	0.3952	ambiguous	-1.102	Destabilizing	0.967	D	0.695	prob.neutral	N	0.499021915	None	None	N
I/G	0.9733	likely_pathogenic	0.9566	pathogenic	-2.183	Highly Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	N
I/H	0.9731	likely_pathogenic	0.9688	pathogenic	-1.389	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
I/K	0.9633	likely_pathogenic	0.9546	pathogenic	-1.347	Destabilizing	0.853	D	0.832	deleterious	None	None	None	None	N
I/L	0.2744	likely_benign	0.2359	benign	-0.777	Destabilizing	0.053	N	0.434	neutral	N	0.492069701	None	None	N
I/M	0.2027	likely_benign	0.1731	benign	-0.614	Destabilizing	0.898	D	0.689	prob.neutral	N	0.515342198	None	None	N
I/N	0.9058	likely_pathogenic	0.8829	pathogenic	-1.234	Destabilizing	0.998	D	0.85	deleterious	D	0.552057687	None	None	N
I/P	0.9751	likely_pathogenic	0.9664	pathogenic	-1.088	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	N
I/Q	0.9654	likely_pathogenic	0.9588	pathogenic	-1.322	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
I/R	0.9509	likely_pathogenic	0.9401	pathogenic	-0.815	Destabilizing	0.987	D	0.849	deleterious	None	None	None	None	N
I/S	0.9106	likely_pathogenic	0.8786	pathogenic	-1.859	Destabilizing	0.987	D	0.812	deleterious	D	0.540447892	None	None	N
I/T	0.8257	likely_pathogenic	0.7898	pathogenic	-1.67	Destabilizing	0.863	D	0.711	prob.delet.	N	0.519456801	None	None	N
I/V	0.1049	likely_benign	0.0996	benign	-1.088	Destabilizing	None	N	0.255	neutral	N	0.411895628	None	None	N
I/W	0.966	likely_pathogenic	0.9601	pathogenic	-1.252	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
I/Y	0.8535	likely_pathogenic	0.8461	pathogenic	-1.021	Destabilizing	0.902	D	0.763	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.