TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8092	24499;24500;24501	chr2:178718926;178718925;178718924	chr2:179583653;179583652;179583651
N2AB	7775	23548;23549;23550	chr2:178718926;178718925;178718924	chr2:179583653;179583652;179583651
N2A	6848	20767;20768;20769	chr2:178718926;178718925;178718924	chr2:179583653;179583652;179583651
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-66
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.339
• 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/E	None	None	0.085	D	0.526	0.515	0.577006569591	gnomAD-4.0.0	1.5952E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86416E-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	0.335	likely_benign	0.3221	benign	-0.48	Destabilizing	0.865	D	0.601	neutral	D	0.634273376	None	None	I
G/C	0.5957	likely_pathogenic	0.5687	pathogenic	-0.896	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
G/D	0.2663	likely_benign	0.2834	benign	-1.003	Destabilizing	0.895	D	0.663	neutral	None	None	None	None	I
G/E	0.3068	likely_benign	0.3129	benign	-1.155	Destabilizing	0.085	N	0.526	neutral	D	0.611501599	None	None	I
G/F	0.7953	likely_pathogenic	0.8054	pathogenic	-1.13	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
G/H	0.5112	ambiguous	0.5165	ambiguous	-0.825	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	I
G/I	0.8115	likely_pathogenic	0.8119	pathogenic	-0.504	Destabilizing	0.992	D	0.748	deleterious	None	None	None	None	I
G/K	0.4937	ambiguous	0.4792	ambiguous	-1.129	Destabilizing	0.968	D	0.681	prob.neutral	None	None	None	None	I
G/L	0.7268	likely_pathogenic	0.7261	pathogenic	-0.504	Destabilizing	0.983	D	0.711	prob.delet.	None	None	None	None	I
G/M	0.763	likely_pathogenic	0.76	pathogenic	-0.408	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
G/N	0.3367	likely_benign	0.3326	benign	-0.734	Destabilizing	0.185	N	0.339	neutral	None	None	None	None	I
G/P	0.9661	likely_pathogenic	0.9718	pathogenic	-0.46	Destabilizing	0.992	D	0.723	prob.delet.	None	None	None	None	I
G/Q	0.4164	ambiguous	0.4192	ambiguous	-1.046	Destabilizing	0.968	D	0.701	prob.neutral	None	None	None	None	I
G/R	0.3742	ambiguous	0.3609	ambiguous	-0.615	Destabilizing	0.978	D	0.703	prob.neutral	D	0.634475181	None	None	I
G/S	0.1898	likely_benign	0.1787	benign	-0.86	Destabilizing	0.895	D	0.624	neutral	None	None	None	None	I
G/T	0.4339	ambiguous	0.4139	ambiguous	-0.95	Destabilizing	0.983	D	0.684	prob.neutral	None	None	None	None	I
G/V	0.6833	likely_pathogenic	0.6753	pathogenic	-0.46	Destabilizing	0.978	D	0.712	prob.delet.	D	0.634676985	None	None	I
G/W	0.6735	likely_pathogenic	0.6959	pathogenic	-1.316	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	I
G/Y	0.6488	likely_pathogenic	0.6729	pathogenic	-0.975	Destabilizing	0.999	D	0.759	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.