TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32880	98863;98864;98865	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
N2AB	31239	93940;93941;93942	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
N2A	30312	91159;91160;91161	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
N2B	23815	71668;71669;71670	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
Novex-1	23940	72043;72044;72045	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
Novex-2	24007	72244;72245;72246	chr2:178539427;178539426;178539425	chr2:179404154;179404153;179404152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-127
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.7662
• 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
K/R	None	None	0.006	N	0.211	0.044	0.171388866994	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
K/A	0.254	likely_benign	0.2524	benign	-0.05	Destabilizing	0.86	D	0.621	neutral	None	None	None	None	N
K/C	0.6221	likely_pathogenic	0.6027	pathogenic	-0.296	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
K/D	0.4079	ambiguous	0.398	ambiguous	-0.065	Destabilizing	0.978	D	0.656	neutral	None	None	None	None	N
K/E	0.1573	likely_benign	0.156	benign	-0.082	Destabilizing	0.822	D	0.61	neutral	N	0.346805921	None	None	N
K/F	0.6499	likely_pathogenic	0.6351	pathogenic	-0.4	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.3576	ambiguous	0.3355	benign	-0.198	Destabilizing	0.956	D	0.613	neutral	None	None	None	None	N
K/H	0.2911	likely_benign	0.2796	benign	-0.468	Destabilizing	0.994	D	0.66	neutral	None	None	None	None	N
K/I	0.2865	likely_benign	0.279	benign	0.254	Stabilizing	0.971	D	0.742	deleterious	N	0.474580804	None	None	N
K/L	0.2692	likely_benign	0.2642	benign	0.254	Stabilizing	0.956	D	0.613	neutral	None	None	None	None	N
K/M	0.2303	likely_benign	0.2256	benign	0.144	Stabilizing	0.998	D	0.65	neutral	None	None	None	None	N
K/N	0.3122	likely_benign	0.2978	benign	0.151	Stabilizing	0.942	D	0.647	neutral	N	0.435697129	None	None	N
K/P	0.3859	ambiguous	0.3879	ambiguous	0.178	Stabilizing	0.993	D	0.668	neutral	None	None	None	None	N
K/Q	0.1292	likely_benign	0.1274	benign	-0.055	Destabilizing	0.942	D	0.663	neutral	N	0.408318526	None	None	N
K/R	0.0857	likely_benign	0.0826	benign	-0.042	Destabilizing	0.006	N	0.211	neutral	N	0.422863904	None	None	N
K/S	0.2986	likely_benign	0.29	benign	-0.305	Destabilizing	0.86	D	0.657	neutral	None	None	None	None	N
K/T	0.1684	likely_benign	0.1693	benign	-0.19	Destabilizing	0.942	D	0.627	neutral	N	0.464806527	None	None	N
K/V	0.2594	likely_benign	0.2609	benign	0.178	Stabilizing	0.978	D	0.701	prob.neutral	None	None	None	None	N
K/W	0.6873	likely_pathogenic	0.6632	pathogenic	-0.428	Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
K/Y	0.5279	ambiguous	0.5089	ambiguous	-0.065	Destabilizing	0.993	D	0.737	prob.delet.	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.