TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16795	50608;50609;50610	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
N2AB	15154	45685;45686;45687	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
N2A	14227	42904;42905;42906	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
N2B	7730	23413;23414;23415	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
Novex-1	7855	23788;23789;23790	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
Novex-2	7922	23989;23990;23991	chr2:178611926;178611925;178611924	chr2:179476653;179476652;179476651
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: Fn3-10
• Domain position: 45
• Structural Position: 62
• Q(SASA): 0.2662
• Predicted PPI site: N

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/V	None	None	0.997	N	0.711	0.4	0.75671349718	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.2658	likely_benign	0.2473	benign	-0.296	Destabilizing	0.604	D	0.477	neutral	N	0.484797714	None	None	N
G/C	0.7158	likely_pathogenic	0.6553	pathogenic	-0.939	Destabilizing	1.0	D	0.775	deleterious	D	0.580664181	None	None	N
G/D	0.8564	likely_pathogenic	0.8249	pathogenic	-0.649	Destabilizing	0.999	D	0.654	neutral	N	0.481183614	None	None	N
G/E	0.8612	likely_pathogenic	0.8142	pathogenic	-0.813	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
G/F	0.9502	likely_pathogenic	0.9367	pathogenic	-1.008	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/H	0.9184	likely_pathogenic	0.8964	pathogenic	-0.476	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/I	0.8821	likely_pathogenic	0.8684	pathogenic	-0.471	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/K	0.9634	likely_pathogenic	0.9444	pathogenic	-0.872	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
G/L	0.851	likely_pathogenic	0.8309	pathogenic	-0.471	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
G/M	0.8986	likely_pathogenic	0.8808	pathogenic	-0.573	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/N	0.7577	likely_pathogenic	0.7419	pathogenic	-0.523	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
G/P	0.978	likely_pathogenic	0.9815	pathogenic	-0.382	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
G/Q	0.8678	likely_pathogenic	0.8233	pathogenic	-0.809	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/R	0.9216	likely_pathogenic	0.8952	pathogenic	-0.401	Destabilizing	0.999	D	0.744	deleterious	N	0.484593998	None	None	N
G/S	0.2807	likely_benign	0.2515	benign	-0.653	Destabilizing	0.997	D	0.603	neutral	N	0.444451443	None	None	N
G/T	0.599	likely_pathogenic	0.5537	ambiguous	-0.749	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
G/V	0.7623	likely_pathogenic	0.7227	pathogenic	-0.382	Destabilizing	0.997	D	0.711	prob.delet.	N	0.478394945	None	None	N
G/W	0.9451	likely_pathogenic	0.9254	pathogenic	-1.145	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/Y	0.9439	likely_pathogenic	0.9285	pathogenic	-0.818	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N

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.