TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9369	28330;28331;28332	chr2:178711131;178711130;178711129	chr2:179575858;179575857;179575856
N2AB	9052	27379;27380;27381	chr2:178711131;178711130;178711129	chr2:179575858;179575857;179575856
N2A	8125	24598;24599;24600	chr2:178711131;178711130;178711129	chr2:179575858;179575857;179575856
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-79
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2253
• 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/D	None	None	1.0	None	0.832	0.728	0.6296786883	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
G/S	None	None	1.0	None	0.836	0.687	0.568643509186	gnomAD-4.0.0	1.59134E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85847E-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	0.3376	likely_benign	0.3875	ambiguous	-0.659	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
G/C	0.8566	likely_pathogenic	0.8631	pathogenic	-0.768	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/D	0.9022	likely_pathogenic	0.9252	pathogenic	-1.176	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
G/E	0.9179	likely_pathogenic	0.9384	pathogenic	-1.182	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/F	0.9748	likely_pathogenic	0.9813	pathogenic	-0.871	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/H	0.9681	likely_pathogenic	0.9749	pathogenic	-1.438	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
G/I	0.9638	likely_pathogenic	0.9742	pathogenic	-0.09	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
G/K	0.9711	likely_pathogenic	0.9763	pathogenic	-1.226	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/L	0.9494	likely_pathogenic	0.9592	pathogenic	-0.09	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/M	0.9705	likely_pathogenic	0.9768	pathogenic	-0.078	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/N	0.9306	likely_pathogenic	0.9392	pathogenic	-0.945	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/P	0.9953	likely_pathogenic	0.997	pathogenic	-0.236	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/Q	0.9295	likely_pathogenic	0.9446	pathogenic	-1.035	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/R	0.9172	likely_pathogenic	0.9375	pathogenic	-1.01	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/S	0.3679	ambiguous	0.4044	ambiguous	-1.237	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
G/T	0.8528	likely_pathogenic	0.8724	pathogenic	-1.15	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/V	0.9088	likely_pathogenic	0.9338	pathogenic	-0.236	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/W	0.9677	likely_pathogenic	0.9777	pathogenic	-1.361	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/Y	0.9702	likely_pathogenic	0.98	pathogenic	-0.878	Destabilizing	1.0	D	0.781	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.