TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6360	19303;19304;19305	chr2:178728960;178728959;178728958	chr2:179593687;179593686;179593685
N2AB	6043	18352;18353;18354	chr2:178728960;178728959;178728958	chr2:179593687;179593686;179593685
N2A	5116	15571;15572;15573	chr2:178728960;178728959;178728958	chr2:179593687;179593686;179593685
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-47
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1656
• 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	rs900886438	None	1.0	D	0.842	0.731	0.77098309394	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	6.07533E-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
G/A	0.361	ambiguous	0.3821	ambiguous	-0.393	Destabilizing	1.0	D	0.745	deleterious	D	0.579345025	None	None	I
G/C	0.7999	likely_pathogenic	0.8129	pathogenic	-0.487	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
G/D	0.8241	likely_pathogenic	0.8333	pathogenic	-0.677	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/E	0.9101	likely_pathogenic	0.9147	pathogenic	-0.593	Destabilizing	1.0	D	0.842	deleterious	D	0.6648209	None	None	I
G/F	0.9775	likely_pathogenic	0.9786	pathogenic	-0.544	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
G/H	0.9488	likely_pathogenic	0.9521	pathogenic	-1.364	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
G/I	0.9753	likely_pathogenic	0.9766	pathogenic	0.455	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/K	0.9445	likely_pathogenic	0.948	pathogenic	-0.614	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
G/L	0.9582	likely_pathogenic	0.9618	pathogenic	0.455	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/M	0.9699	likely_pathogenic	0.9708	pathogenic	0.323	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/N	0.8644	likely_pathogenic	0.8716	pathogenic	-0.559	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/P	0.9974	likely_pathogenic	0.9974	pathogenic	0.218	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
G/Q	0.8898	likely_pathogenic	0.8965	pathogenic	-0.47	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/R	0.8589	likely_pathogenic	0.8708	pathogenic	-0.747	Destabilizing	1.0	D	0.834	deleterious	D	0.664619096	None	None	I
G/S	0.312	likely_benign	0.3232	benign	-0.986	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/T	0.8527	likely_pathogenic	0.8611	pathogenic	-0.778	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/V	0.9405	likely_pathogenic	0.9438	pathogenic	0.218	Stabilizing	1.0	D	0.825	deleterious	D	0.648801539	None	None	I
G/W	0.9662	likely_pathogenic	0.9645	pathogenic	-1.183	Destabilizing	1.0	D	0.776	deleterious	D	0.665022705	None	None	I
G/Y	0.9688	likely_pathogenic	0.9688	pathogenic	-0.567	Destabilizing	1.0	D	0.783	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.