TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22013	66262;66263;66264	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
N2AB	20372	61339;61340;61341	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
N2A	19445	58558;58559;58560	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
N2B	12948	39067;39068;39069	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
Novex-1	13073	39442;39443;39444	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
Novex-2	13140	39643;39644;39645	chr2:178582419;178582418;178582417	chr2:179447146;179447145;179447144
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-47
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.1747
• 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/I	rs2047988324	None	0.999	N	0.733	0.439	0.491996647052	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs2047988324	None	0.999	N	0.733	0.439	0.491996647052	gnomAD-4.0.0	3.84754E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18608E-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
T/A	0.1478	likely_benign	0.1303	benign	-0.729	Destabilizing	0.981	D	0.488	neutral	N	0.49209684	None	None	N
T/C	0.355	ambiguous	0.3108	benign	-0.229	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/D	0.7798	likely_pathogenic	0.734	pathogenic	-0.147	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
T/E	0.6668	likely_pathogenic	0.6192	pathogenic	0.003	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
T/F	0.5777	likely_pathogenic	0.5282	ambiguous	-0.741	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/G	0.4512	ambiguous	0.3657	ambiguous	-1.082	Destabilizing	0.997	D	0.597	neutral	None	None	None	None	N
T/H	0.4476	ambiguous	0.4102	ambiguous	-1.125	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/I	0.3737	ambiguous	0.3487	ambiguous	0.171	Stabilizing	0.999	D	0.733	prob.delet.	N	0.489565626	None	None	N
T/K	0.2871	likely_benign	0.2882	benign	0.151	Stabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
T/L	0.094	likely_benign	0.0963	benign	0.171	Stabilizing	0.998	D	0.57	neutral	None	None	None	None	N
T/M	0.128	likely_benign	0.1172	benign	0.052	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
T/N	0.2232	likely_benign	0.186	benign	-0.379	Destabilizing	0.999	D	0.631	neutral	N	0.511747617	None	None	N
T/P	0.1664	likely_benign	0.1437	benign	-0.098	Destabilizing	0.999	D	0.737	prob.delet.	N	0.475055769	None	None	N
T/Q	0.3559	ambiguous	0.3079	benign	-0.216	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/R	0.2421	likely_benign	0.2305	benign	0.002	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/S	0.2419	likely_benign	0.1982	benign	-0.712	Destabilizing	0.905	D	0.429	neutral	N	0.48753771	None	None	N
T/V	0.2418	likely_benign	0.2294	benign	-0.098	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	N
T/W	0.8845	likely_pathogenic	0.8613	pathogenic	-0.84	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/Y	0.5723	likely_pathogenic	0.5249	ambiguous	-0.415	Destabilizing	1.0	D	0.799	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.