TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17656	53191;53192;53193	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
N2AB	16015	48268;48269;48270	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
N2A	15088	45487;45488;45489	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
N2B	8591	25996;25997;25998	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
Novex-1	8716	26371;26372;26373	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
Novex-2	8783	26572;26573;26574	chr2:178607821;178607820;178607819	chr2:179472548;179472547;179472546
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: Fn3-16
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.2122
• 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/R	rs1269389543	None	1.0	N	0.813	0.435	0.582701273649	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/R	rs1269389543	None	1.0	N	0.813	0.435	0.582701273649	gnomAD-4.0.0	6.20024E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47943E-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	0.1688	likely_benign	0.1683	benign	-0.865	Destabilizing	1.0	D	0.693	prob.neutral	N	0.439969585	None	None	N
G/C	0.5048	ambiguous	0.5211	ambiguous	-0.979	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/D	0.8651	likely_pathogenic	0.8785	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/E	0.8066	likely_pathogenic	0.82	pathogenic	-2.028	Highly Destabilizing	1.0	D	0.816	deleterious	N	0.465807425	None	None	N
G/F	0.9239	likely_pathogenic	0.9298	pathogenic	-0.914	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
G/H	0.9249	likely_pathogenic	0.9296	pathogenic	-1.73	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/I	0.8081	likely_pathogenic	0.8365	pathogenic	-0.253	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/K	0.916	likely_pathogenic	0.9196	pathogenic	-1.443	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/L	0.8513	likely_pathogenic	0.861	pathogenic	-0.253	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
G/M	0.8595	likely_pathogenic	0.8701	pathogenic	-0.319	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/N	0.8874	likely_pathogenic	0.9	pathogenic	-1.296	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
G/P	0.9936	likely_pathogenic	0.9947	pathogenic	-0.417	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/Q	0.8414	likely_pathogenic	0.8484	pathogenic	-1.371	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/R	0.8004	likely_pathogenic	0.8057	pathogenic	-1.251	Destabilizing	1.0	D	0.813	deleterious	N	0.454033046	None	None	N
G/S	0.2593	likely_benign	0.2662	benign	-1.493	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/T	0.5567	ambiguous	0.5976	pathogenic	-1.397	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/V	0.6086	likely_pathogenic	0.6507	pathogenic	-0.417	Destabilizing	1.0	D	0.829	deleterious	N	0.453019088	None	None	N
G/W	0.9026	likely_pathogenic	0.9118	pathogenic	-1.498	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/Y	0.9045	likely_pathogenic	0.912	pathogenic	-1.032	Destabilizing	1.0	D	0.827	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.