TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26058	78397;78398;78399	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
N2AB	24417	73474;73475;73476	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
N2A	23490	70693;70694;70695	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
N2B	16993	51202;51203;51204	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
Novex-1	17118	51577;51578;51579	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
Novex-2	17185	51778;51779;51780	chr2:178567960;178567959;178567958	chr2:179432687;179432686;179432685
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-77
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4191
• 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/S	None	None	0.568	N	0.485	0.38	0.333154297509	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-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	0.6003	likely_pathogenic	0.7165	pathogenic	-0.658	Destabilizing	0.955	D	0.618	neutral	N	0.506663285	None	None	N
G/C	0.7265	likely_pathogenic	0.7988	pathogenic	-0.926	Destabilizing	1.0	D	0.853	deleterious	D	0.556256017	None	None	N
G/D	0.6968	likely_pathogenic	0.7849	pathogenic	-1.2	Destabilizing	0.235	N	0.487	neutral	N	0.496268031	None	None	N
G/E	0.8446	likely_pathogenic	0.9051	pathogenic	-1.303	Destabilizing	0.99	D	0.771	deleterious	None	None	None	None	N
G/F	0.9535	likely_pathogenic	0.9653	pathogenic	-1.056	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/H	0.926	likely_pathogenic	0.9485	pathogenic	-1.093	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
G/I	0.9553	likely_pathogenic	0.9719	pathogenic	-0.473	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
G/K	0.9684	likely_pathogenic	0.9791	pathogenic	-1.371	Destabilizing	0.995	D	0.838	deleterious	None	None	None	None	N
G/L	0.9398	likely_pathogenic	0.9575	pathogenic	-0.473	Destabilizing	0.995	D	0.828	deleterious	None	None	None	None	N
G/M	0.9302	likely_pathogenic	0.9509	pathogenic	-0.419	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/N	0.5865	likely_pathogenic	0.6833	pathogenic	-0.996	Destabilizing	0.99	D	0.819	deleterious	None	None	None	None	N
G/P	0.9961	likely_pathogenic	0.9976	pathogenic	-0.496	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
G/Q	0.9173	likely_pathogenic	0.9488	pathogenic	-1.249	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
G/R	0.9417	likely_pathogenic	0.9629	pathogenic	-0.891	Destabilizing	0.993	D	0.875	deleterious	D	0.537048898	None	None	N
G/S	0.3791	ambiguous	0.5035	ambiguous	-1.168	Destabilizing	0.568	D	0.485	neutral	N	0.505649327	None	None	N
G/T	0.769	likely_pathogenic	0.8521	pathogenic	-1.206	Destabilizing	0.99	D	0.835	deleterious	None	None	None	None	N
G/V	0.9035	likely_pathogenic	0.9441	pathogenic	-0.496	Destabilizing	0.993	D	0.831	deleterious	D	0.537809367	None	None	N
G/W	0.9194	likely_pathogenic	0.9428	pathogenic	-1.331	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/Y	0.9043	likely_pathogenic	0.9243	pathogenic	-0.973	Destabilizing	1.0	D	0.866	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.