TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16293	49102;49103;49104	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
N2AB	14652	44179;44180;44181	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
N2A	13725	41398;41399;41400	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
N2B	7228	21907;21908;21909	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
Novex-1	7353	22282;22283;22284	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
Novex-2	7420	22483;22484;22485	chr2:178614637;178614636;178614635	chr2:179479364;179479363;179479362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-110
• Domain position: 32
• Structural Position: 49
• Q(SASA): 0.1592
• 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
T/K	None	None	0.993	N	0.722	0.362	0.368369118721	gnomAD-4.0.0	1.44039E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.575E-05	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
T/A	0.257	likely_benign	0.2726	benign	-1.082	Destabilizing	0.977	D	0.515	neutral	N	0.447762569	None	None	N
T/C	0.573	likely_pathogenic	0.6127	pathogenic	-0.625	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/D	0.8861	likely_pathogenic	0.8919	pathogenic	-0.794	Destabilizing	0.99	D	0.711	prob.delet.	None	None	None	None	N
T/E	0.6894	likely_pathogenic	0.6984	pathogenic	-0.628	Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
T/F	0.4836	ambiguous	0.521	ambiguous	-0.803	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
T/G	0.4836	ambiguous	0.5082	ambiguous	-1.476	Destabilizing	0.966	D	0.631	neutral	None	None	None	None	N
T/H	0.3137	likely_benign	0.3496	ambiguous	-1.608	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
T/I	0.497	ambiguous	0.5158	ambiguous	-0.064	Destabilizing	0.999	D	0.773	deleterious	N	0.447018324	None	None	N
T/K	0.244	likely_benign	0.2637	benign	-0.355	Destabilizing	0.993	D	0.722	prob.delet.	N	0.451205711	None	None	N
T/L	0.1852	likely_benign	0.1954	benign	-0.064	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
T/M	0.1399	likely_benign	0.1569	benign	-0.056	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/N	0.2468	likely_benign	0.2635	benign	-0.839	Destabilizing	0.289	N	0.387	neutral	None	None	None	None	N
T/P	0.9366	likely_pathogenic	0.9297	pathogenic	-0.371	Destabilizing	0.999	D	0.759	deleterious	D	0.607962447	None	None	N
T/Q	0.3	likely_benign	0.3211	benign	-0.692	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
T/R	0.2313	likely_benign	0.2473	benign	-0.543	Destabilizing	0.993	D	0.775	deleterious	N	0.450922572	None	None	N
T/S	0.2222	likely_benign	0.2367	benign	-1.145	Destabilizing	0.955	D	0.522	neutral	N	0.450367325	None	None	N
T/V	0.3591	ambiguous	0.3719	ambiguous	-0.371	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
T/W	0.7553	likely_pathogenic	0.7795	pathogenic	-0.863	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/Y	0.4186	ambiguous	0.4509	ambiguous	-0.51	Destabilizing	0.999	D	0.803	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.