TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8010	24253;24254;24255	chr2:178719362;178719361;178719360	chr2:179584089;179584088;179584087
N2AB	7693	23302;23303;23304	chr2:178719362;178719361;178719360	chr2:179584089;179584088;179584087
N2A	6766	20521;20522;20523	chr2:178719362;178719361;178719360	chr2:179584089;179584088;179584087
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-65
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4319
• 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	D	0.812	0.595	0.645590637679	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/R	None	None	1.0	D	0.792	0.617	0.814818510161	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.6306	likely_pathogenic	0.6829	pathogenic	-0.173	Destabilizing	1.0	D	0.79	deleterious	D	0.575769679	None	None	I
G/C	0.9381	likely_pathogenic	0.9517	pathogenic	-0.851	Destabilizing	1.0	D	0.696	prob.neutral	D	0.6472049520000001	None	None	I
G/D	0.9832	likely_pathogenic	0.9879	pathogenic	-0.396	Destabilizing	1.0	D	0.812	deleterious	D	0.624867144	None	None	I
G/E	0.9871	likely_pathogenic	0.9908	pathogenic	-0.549	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/F	0.9923	likely_pathogenic	0.9932	pathogenic	-0.907	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
G/H	0.9941	likely_pathogenic	0.9949	pathogenic	-0.475	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
G/I	0.9797	likely_pathogenic	0.9843	pathogenic	-0.297	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
G/K	0.9946	likely_pathogenic	0.9957	pathogenic	-0.706	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
G/L	0.9836	likely_pathogenic	0.9867	pathogenic	-0.297	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
G/M	0.9919	likely_pathogenic	0.9937	pathogenic	-0.441	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
G/N	0.9842	likely_pathogenic	0.9875	pathogenic	-0.356	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/P	0.995	likely_pathogenic	0.9957	pathogenic	-0.223	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
G/Q	0.9878	likely_pathogenic	0.9906	pathogenic	-0.603	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/R	0.9779	likely_pathogenic	0.9816	pathogenic	-0.335	Destabilizing	1.0	D	0.792	deleterious	D	0.625674361	None	None	I
G/S	0.674	likely_pathogenic	0.7259	pathogenic	-0.512	Destabilizing	1.0	D	0.829	deleterious	D	0.591637238	None	None	I
G/T	0.9387	likely_pathogenic	0.9512	pathogenic	-0.588	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/V	0.9518	likely_pathogenic	0.9618	pathogenic	-0.223	Destabilizing	1.0	D	0.757	deleterious	D	0.646801344	None	None	I
G/W	0.9891	likely_pathogenic	0.9903	pathogenic	-1.086	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
G/Y	0.9911	likely_pathogenic	0.9929	pathogenic	-0.713	Destabilizing	1.0	D	0.729	prob.delet.	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.