TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9562	28909;28910;28911	chr2:178709635;178709634;178709633	chr2:179574362;179574361;179574360
N2AB	9245	27958;27959;27960	chr2:178709635;178709634;178709633	chr2:179574362;179574361;179574360
N2A	8318	25177;25178;25179	chr2:178709635;178709634;178709633	chr2:179574362;179574361;179574360
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: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-81
• Domain position: 70
• Structural Position: 152
• Q(SASA): 0.2056
• 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/S	rs1445369813	None	1.0	None	0.83	0.649	0.548145191872	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4548	ambiguous	0.5784	pathogenic	-0.567	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
G/C	0.8724	likely_pathogenic	0.9139	pathogenic	-0.788	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/D	0.945	likely_pathogenic	0.9616	pathogenic	-0.689	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/E	0.9651	likely_pathogenic	0.9751	pathogenic	-0.729	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/F	0.9854	likely_pathogenic	0.9875	pathogenic	-0.879	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/H	0.9901	likely_pathogenic	0.9932	pathogenic	-1.196	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
G/I	0.9825	likely_pathogenic	0.9865	pathogenic	-0.137	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/K	0.9943	likely_pathogenic	0.9957	pathogenic	-1.019	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/L	0.9759	likely_pathogenic	0.9821	pathogenic	-0.137	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/M	0.9849	likely_pathogenic	0.9898	pathogenic	-0.158	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/N	0.9688	likely_pathogenic	0.9805	pathogenic	-0.738	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.237	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
G/Q	0.9778	likely_pathogenic	0.9841	pathogenic	-0.853	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
G/R	0.9772	likely_pathogenic	0.9801	pathogenic	-0.802	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/S	0.5161	ambiguous	0.6193	pathogenic	-1.063	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/T	0.9345	likely_pathogenic	0.9579	pathogenic	-1.006	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/V	0.9535	likely_pathogenic	0.9639	pathogenic	-0.237	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
G/W	0.9864	likely_pathogenic	0.9867	pathogenic	-1.275	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
G/Y	0.986	likely_pathogenic	0.9882	pathogenic	-0.811	Destabilizing	1.0	D	0.762	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.