TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27847	83764;83765;83766	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
N2AB	26206	78841;78842;78843	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
N2A	25279	76060;76061;76062	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
N2B	18782	56569;56570;56571	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
Novex-1	18907	56944;56945;56946	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
Novex-2	18974	57145;57146;57147	chr2:178562593;178562592;178562591	chr2:179427320;179427319;179427318
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-90
• Domain position: 82
• Structural Position: 115
• Q(SASA): 0.2385
• 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
G/R	None	None	1.0	D	0.923	0.74	0.745218052487	gnomAD-4.0.0	2.05684E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70075E-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
G/A	0.9021	likely_pathogenic	0.9203	pathogenic	-0.543	Destabilizing	0.999	D	0.761	deleterious	D	0.551433851	None	None	I
G/C	0.9581	likely_pathogenic	0.9678	pathogenic	-0.994	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
G/D	0.9867	likely_pathogenic	0.9898	pathogenic	-0.363	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	I
G/E	0.992	likely_pathogenic	0.9937	pathogenic	-0.507	Destabilizing	1.0	D	0.913	deleterious	D	0.558524196	None	None	I
G/F	0.9955	likely_pathogenic	0.9965	pathogenic	-1.158	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/H	0.9931	likely_pathogenic	0.9945	pathogenic	-0.73	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/I	0.9934	likely_pathogenic	0.995	pathogenic	-0.597	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	I
G/K	0.995	likely_pathogenic	0.9961	pathogenic	-0.793	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
G/L	0.991	likely_pathogenic	0.9922	pathogenic	-0.597	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
G/M	0.9958	likely_pathogenic	0.9967	pathogenic	-0.566	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/N	0.9834	likely_pathogenic	0.9864	pathogenic	-0.492	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/P	0.9991	likely_pathogenic	0.9993	pathogenic	-0.545	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	I
G/Q	0.9878	likely_pathogenic	0.9891	pathogenic	-0.763	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	I
G/R	0.9811	likely_pathogenic	0.9837	pathogenic	-0.391	Destabilizing	1.0	D	0.923	deleterious	D	0.569880501	None	None	I
G/S	0.8069	likely_pathogenic	0.8342	pathogenic	-0.739	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/T	0.9722	likely_pathogenic	0.9765	pathogenic	-0.804	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
G/V	0.9875	likely_pathogenic	0.9901	pathogenic	-0.545	Destabilizing	1.0	D	0.896	deleterious	D	0.533329596	None	None	I
G/W	0.9936	likely_pathogenic	0.9953	pathogenic	-1.276	Destabilizing	1.0	D	0.887	deleterious	D	0.57064097	None	None	I
G/Y	0.9931	likely_pathogenic	0.9948	pathogenic	-0.937	Destabilizing	1.0	D	0.897	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.