TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26650	80173;80174;80175	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
N2AB	25009	75250;75251;75252	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
N2A	24082	72469;72470;72471	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
N2B	17585	52978;52979;52980	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
Novex-1	17710	53353;53354;53355	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
Novex-2	17777	53554;53555;53556	chr2:178566184;178566183;178566182	chr2:179430911;179430910;179430909
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-138
• Domain position: 57
• Structural Position: 140
• Q(SASA): 0.1584
• 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	None	None	0.333	D	0.237	0.459	0.514472708086	gnomAD-4.0.0	3.42128E-06	None	None	None	None	N	None	2.989E-05	0	None	0	0	None	0	0	2.6986E-06	1.15937E-05	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	0.758	likely_pathogenic	0.6903	pathogenic	-2.748	Highly Destabilizing	0.992	D	0.666	neutral	None	None	None	None	N
I/C	0.9063	likely_pathogenic	0.8917	pathogenic	-2.489	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
I/D	0.9941	likely_pathogenic	0.9916	pathogenic	-3.112	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
I/E	0.9798	likely_pathogenic	0.9706	pathogenic	-2.933	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/F	0.3435	ambiguous	0.3075	benign	-1.822	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
I/G	0.9747	likely_pathogenic	0.9637	pathogenic	-3.265	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
I/H	0.9663	likely_pathogenic	0.9551	pathogenic	-2.59	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
I/K	0.9455	likely_pathogenic	0.9264	pathogenic	-2.217	Highly Destabilizing	0.999	D	0.845	deleterious	D	0.641986607	None	None	N
I/L	0.1831	likely_benign	0.1678	benign	-1.271	Destabilizing	0.889	D	0.422	neutral	D	0.539280545	None	None	N
I/M	0.1308	likely_benign	0.1219	benign	-1.344	Destabilizing	0.998	D	0.689	prob.neutral	D	0.615035865	None	None	N
I/N	0.9403	likely_pathogenic	0.9186	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/P	0.9914	likely_pathogenic	0.9887	pathogenic	-1.743	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
I/Q	0.9486	likely_pathogenic	0.9316	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/R	0.9156	likely_pathogenic	0.8853	pathogenic	-1.755	Destabilizing	0.999	D	0.852	deleterious	D	0.641986607	None	None	N
I/S	0.8702	likely_pathogenic	0.8311	pathogenic	-3.237	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
I/T	0.6539	likely_pathogenic	0.5554	ambiguous	-2.909	Highly Destabilizing	0.989	D	0.742	deleterious	D	0.641582998	None	None	N
I/V	0.0998	likely_benign	0.0921	benign	-1.743	Destabilizing	0.333	N	0.237	neutral	D	0.563404172	None	None	N
I/W	0.9315	likely_pathogenic	0.9233	pathogenic	-2.124	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/Y	0.8838	likely_pathogenic	0.868	pathogenic	-1.888	Destabilizing	1.0	D	0.736	prob.delet.	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.