TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9669	29230;29231;29232	chr2:178707562;178707561;178707560	chr2:179572289;179572288;179572287
N2AB	9352	28279;28280;28281	chr2:178707562;178707561;178707560	chr2:179572289;179572288;179572287
N2A	8425	25498;25499;25500	chr2:178707562;178707561;178707560	chr2:179572289;179572288;179572287
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-82
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.3036
• 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	None	0.859	0.806	0.874896931464	gnomAD-4.0.0	5.47421E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19625E-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	0.885	likely_pathogenic	0.6014	pathogenic	-0.267	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
G/C	0.9775	likely_pathogenic	0.8682	pathogenic	-0.892	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/D	0.9838	likely_pathogenic	0.9022	pathogenic	-0.57	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/E	0.989	likely_pathogenic	0.9239	pathogenic	-0.742	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/F	0.9943	likely_pathogenic	0.9686	pathogenic	-1.08	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/H	0.9941	likely_pathogenic	0.958	pathogenic	-0.438	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/I	0.9958	likely_pathogenic	0.9631	pathogenic	-0.507	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/K	0.9926	likely_pathogenic	0.9527	pathogenic	-0.654	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/L	0.9938	likely_pathogenic	0.9562	pathogenic	-0.507	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/M	0.9968	likely_pathogenic	0.9728	pathogenic	-0.5	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/N	0.9853	likely_pathogenic	0.9006	pathogenic	-0.355	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9976	pathogenic	-0.398	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/Q	0.9887	likely_pathogenic	0.9249	pathogenic	-0.661	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/R	0.9769	likely_pathogenic	0.8797	pathogenic	-0.21	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/S	0.8439	likely_pathogenic	0.4807	ambiguous	-0.48	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/T	0.9817	likely_pathogenic	0.8674	pathogenic	-0.588	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/V	0.9882	likely_pathogenic	0.915	pathogenic	-0.398	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/W	0.9932	likely_pathogenic	0.9609	pathogenic	-1.189	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/Y	0.9926	likely_pathogenic	0.9552	pathogenic	-0.854	Destabilizing	1.0	D	0.836	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.