TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8157	24694;24695;24696	chr2:178718731;178718730;178718729	chr2:179583458;179583457;179583456
N2AB	7840	23743;23744;23745	chr2:178718731;178718730;178718729	chr2:179583458;179583457;179583456
N2A	6913	20962;20963;20964	chr2:178718731;178718730;178718729	chr2:179583458;179583457;179583456
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: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-66
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2242
• 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	rs753025964	-0.455	1.0	D	0.789	0.627	0.546562531242	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
G/S	rs753025964	-0.455	1.0	D	0.789	0.627	0.546562531242	gnomAD-4.0.0	1.64213E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.15877E-05	0	0
G/V	None	None	1.0	D	0.819	0.691	0.933750783859	gnomAD-4.0.0	1.59131E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85842E-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	0.5911	likely_pathogenic	0.5763	pathogenic	-0.243	Destabilizing	1.0	D	0.734	prob.delet.	D	0.616623529	None	None	I
G/C	0.8997	likely_pathogenic	0.8816	pathogenic	-0.77	Destabilizing	1.0	D	0.798	deleterious	D	0.643372466	None	None	I
G/D	0.8727	likely_pathogenic	0.8207	pathogenic	-0.726	Destabilizing	1.0	D	0.843	deleterious	D	0.61621992	None	None	I
G/E	0.9084	likely_pathogenic	0.8758	pathogenic	-0.908	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/F	0.9718	likely_pathogenic	0.9575	pathogenic	-1.143	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/H	0.961	likely_pathogenic	0.9376	pathogenic	-0.469	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/I	0.9618	likely_pathogenic	0.9532	pathogenic	-0.5	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/K	0.9513	likely_pathogenic	0.9322	pathogenic	-0.637	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/L	0.96	likely_pathogenic	0.95	pathogenic	-0.5	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/M	0.9719	likely_pathogenic	0.9633	pathogenic	-0.399	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/N	0.9148	likely_pathogenic	0.8782	pathogenic	-0.293	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/P	0.9972	likely_pathogenic	0.996	pathogenic	-0.386	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/Q	0.9198	likely_pathogenic	0.8863	pathogenic	-0.64	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/R	0.8862	likely_pathogenic	0.8504	pathogenic	-0.167	Destabilizing	1.0	D	0.851	deleterious	D	0.626344084	None	None	I
G/S	0.5104	ambiguous	0.429	ambiguous	-0.374	Destabilizing	1.0	D	0.789	deleterious	D	0.599998755	None	None	I
G/T	0.8722	likely_pathogenic	0.8285	pathogenic	-0.503	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/V	0.9122	likely_pathogenic	0.8973	pathogenic	-0.386	Destabilizing	1.0	D	0.819	deleterious	D	0.642968858	None	None	I
G/W	0.968	likely_pathogenic	0.9543	pathogenic	-1.257	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/Y	0.9591	likely_pathogenic	0.941	pathogenic	-0.911	Destabilizing	1.0	D	0.824	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.