TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15686	47281;47282;47283	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
N2AB	14045	42358;42359;42360	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
N2A	13118	39577;39578;39579	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
N2B	6621	20086;20087;20088	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
Novex-1	6746	20461;20462;20463	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
Novex-2	6813	20662;20663;20664	chr2:178618402;178618401;178618400	chr2:179483129;179483128;179483127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-1
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.5682
• 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	None	None	1.0	D	0.783	0.538	0.536194329819	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

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	0.5369	ambiguous	0.5244	ambiguous	-0.092	Destabilizing	1.0	D	0.617	neutral	D	0.585522551	None	None	I
G/C	0.6266	likely_pathogenic	0.5937	pathogenic	-0.809	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/D	0.4539	ambiguous	0.5737	pathogenic	-0.309	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
G/E	0.5917	likely_pathogenic	0.6621	pathogenic	-0.466	Destabilizing	1.0	D	0.783	deleterious	D	0.653897981	None	None	I
G/F	0.9314	likely_pathogenic	0.9293	pathogenic	-0.896	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/H	0.8522	likely_pathogenic	0.8846	pathogenic	-0.275	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/I	0.9124	likely_pathogenic	0.8896	pathogenic	-0.354	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
G/K	0.8895	likely_pathogenic	0.9083	pathogenic	-0.385	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/L	0.8887	likely_pathogenic	0.8823	pathogenic	-0.354	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/M	0.9034	likely_pathogenic	0.9029	pathogenic	-0.432	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
G/N	0.5818	likely_pathogenic	0.6469	pathogenic	-0.133	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
G/P	0.9933	likely_pathogenic	0.9933	pathogenic	-0.241	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/Q	0.7216	likely_pathogenic	0.7697	pathogenic	-0.382	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/R	0.8037	likely_pathogenic	0.8321	pathogenic	-0.056	Destabilizing	1.0	D	0.801	deleterious	D	0.630938758	None	None	I
G/S	0.2945	likely_benign	0.3414	ambiguous	-0.277	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
G/T	0.7305	likely_pathogenic	0.7216	pathogenic	-0.366	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
G/V	0.8669	likely_pathogenic	0.838	pathogenic	-0.241	Destabilizing	1.0	D	0.79	deleterious	D	0.749218469	None	None	I
G/W	0.9203	likely_pathogenic	0.925	pathogenic	-1.017	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
G/Y	0.873	likely_pathogenic	0.8793	pathogenic	-0.674	Destabilizing	1.0	D	0.775	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.