TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20010	60253;60254;60255	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
N2AB	18369	55330;55331;55332	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
N2A	17442	52549;52550;52551	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
N2B	10945	33058;33059;33060	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
Novex-1	11070	33433;33434;33435	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
Novex-2	11137	33634;33635;33636	chr2:178591791;178591790;178591789	chr2:179456518;179456517;179456516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-33
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4197
• 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
T/P	None	None	1.0	D	0.838	0.54	0.60587874566	gnomAD-4.0.0	1.59233E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05

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	0.1458	likely_benign	0.1572	benign	-0.387	Destabilizing	0.999	D	0.579	neutral	N	0.485197533	None	None	I
T/C	0.5729	likely_pathogenic	0.6057	pathogenic	-0.266	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
T/D	0.5939	likely_pathogenic	0.6131	pathogenic	0.172	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
T/E	0.4322	ambiguous	0.4405	ambiguous	0.101	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
T/F	0.4196	ambiguous	0.4366	ambiguous	-0.803	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
T/G	0.38	ambiguous	0.4011	ambiguous	-0.534	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
T/H	0.3625	ambiguous	0.3811	ambiguous	-0.804	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
T/I	0.212	likely_benign	0.2398	benign	-0.117	Destabilizing	1.0	D	0.846	deleterious	N	0.515097354	None	None	I
T/K	0.1866	likely_benign	0.19	benign	-0.378	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
T/L	0.1205	likely_benign	0.1352	benign	-0.117	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
T/M	0.1188	likely_benign	0.1277	benign	0.086	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
T/N	0.1936	likely_benign	0.2062	benign	-0.166	Destabilizing	1.0	D	0.832	deleterious	N	0.488502442	None	None	I
T/P	0.5564	ambiguous	0.6129	pathogenic	-0.178	Destabilizing	1.0	D	0.838	deleterious	D	0.529270083	None	None	I
T/Q	0.2713	likely_benign	0.2874	benign	-0.413	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
T/R	0.1767	likely_benign	0.1936	benign	-0.08	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
T/S	0.1545	likely_benign	0.1589	benign	-0.407	Destabilizing	0.999	D	0.587	neutral	N	0.482003501	None	None	I
T/V	0.1815	likely_benign	0.1986	benign	-0.178	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
T/W	0.7313	likely_pathogenic	0.7498	pathogenic	-0.779	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
T/Y	0.4601	ambiguous	0.4838	ambiguous	-0.509	Destabilizing	1.0	D	0.839	deleterious	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.