TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17454	52585;52586;52587	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
N2AB	15813	47662;47663;47664	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
N2A	14886	44881;44882;44883	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
N2B	8389	25390;25391;25392	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
Novex-1	8514	25765;25766;25767	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
Novex-2	8581	25966;25967;25968	chr2:178608651;178608650;178608649	chr2:179473378;179473377;179473376
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: Fn3-14
• Domain position: 86
• Structural Position: 118
• Q(SASA): 0.1439
• 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	0.849	0.834	0.529561333529	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.7492	likely_pathogenic	0.7601	pathogenic	-0.944	Destabilizing	1.0	D	0.693	prob.neutral	D	0.549791691	None	None	I
G/C	0.9581	likely_pathogenic	0.9635	pathogenic	-1.043	Destabilizing	1.0	D	0.827	deleterious	D	0.550805649	None	None	I
G/D	0.9946	likely_pathogenic	0.996	pathogenic	-1.87	Destabilizing	1.0	D	0.849	deleterious	D	0.55029867	None	None	I
G/E	0.9954	likely_pathogenic	0.9962	pathogenic	-1.919	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/F	0.996	likely_pathogenic	0.9967	pathogenic	-1.152	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/H	0.9961	likely_pathogenic	0.9967	pathogenic	-1.557	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/I	0.9946	likely_pathogenic	0.9953	pathogenic	-0.535	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
G/K	0.9986	likely_pathogenic	0.9988	pathogenic	-1.566	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/L	0.9903	likely_pathogenic	0.9918	pathogenic	-0.535	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/M	0.9958	likely_pathogenic	0.9964	pathogenic	-0.421	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/N	0.9924	likely_pathogenic	0.9935	pathogenic	-1.245	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
G/P	0.9989	likely_pathogenic	0.9989	pathogenic	-0.633	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/Q	0.9947	likely_pathogenic	0.9955	pathogenic	-1.456	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/R	0.9956	likely_pathogenic	0.9962	pathogenic	-1.18	Destabilizing	1.0	D	0.887	deleterious	D	0.537928406	None	None	I
G/S	0.5327	ambiguous	0.552	ambiguous	-1.429	Destabilizing	1.0	D	0.799	deleterious	N	0.476603255	None	None	I
G/T	0.9601	likely_pathogenic	0.9664	pathogenic	-1.419	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/V	0.9882	likely_pathogenic	0.9901	pathogenic	-0.633	Destabilizing	1.0	D	0.867	deleterious	D	0.55029867	None	None	I
G/W	0.9956	likely_pathogenic	0.9964	pathogenic	-1.526	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/Y	0.9964	likely_pathogenic	0.997	pathogenic	-1.162	Destabilizing	1.0	D	0.847	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.