TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27471	82636;82637;82638	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
N2AB	25830	77713;77714;77715	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
N2A	24903	74932;74933;74934	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
N2B	18406	55441;55442;55443	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
Novex-1	18531	55816;55817;55818	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
Novex-2	18598	56017;56018;56019	chr2:178563721;178563720;178563719	chr2:179428448;179428447;179428446
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: Fn3-88
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2641
• 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/C	None	None	0.999	D	0.81	0.408	0.730913411271	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	2.23604E-05	None	0	2.52029E-05	None	0	0	0	0	0
G/S	rs757130634	None	0.114	N	0.303	0.113	0.253726318573	gnomAD-4.0.0	8.21048E-06	None	None	None	None	N	None	2.98775E-05	0	None	0	0	None	0	0	9.8942E-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	0.2432	likely_benign	0.2142	benign	-0.822	Destabilizing	0.825	D	0.503	neutral	N	0.490434091	None	None	N
G/C	0.3964	ambiguous	0.3316	benign	-1.185	Destabilizing	0.999	D	0.81	deleterious	D	0.530227453	None	None	N
G/D	0.4942	ambiguous	0.4665	ambiguous	-2.211	Highly Destabilizing	0.988	D	0.706	prob.neutral	N	0.483326078	None	None	N
G/E	0.6001	likely_pathogenic	0.5385	ambiguous	-2.264	Highly Destabilizing	0.991	D	0.695	prob.neutral	None	None	None	None	N
G/F	0.8422	likely_pathogenic	0.8006	pathogenic	-1.238	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
G/H	0.7559	likely_pathogenic	0.6933	pathogenic	-1.342	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/I	0.7258	likely_pathogenic	0.6561	pathogenic	-0.475	Destabilizing	0.995	D	0.828	deleterious	None	None	None	None	N
G/K	0.7577	likely_pathogenic	0.7004	pathogenic	-1.342	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
G/L	0.6508	likely_pathogenic	0.5799	pathogenic	-0.475	Destabilizing	0.991	D	0.777	deleterious	None	None	None	None	N
G/M	0.7734	likely_pathogenic	0.7175	pathogenic	-0.391	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/N	0.5967	likely_pathogenic	0.5745	pathogenic	-1.182	Destabilizing	0.991	D	0.703	prob.neutral	None	None	None	None	N
G/P	0.9683	likely_pathogenic	0.9649	pathogenic	-0.554	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	N
G/Q	0.6935	likely_pathogenic	0.6273	pathogenic	-1.439	Destabilizing	0.991	D	0.804	deleterious	None	None	None	None	N
G/R	0.6897	likely_pathogenic	0.6074	pathogenic	-0.973	Destabilizing	0.988	D	0.794	deleterious	N	0.510855751	None	None	N
G/S	0.1583	likely_benign	0.1486	benign	-1.308	Destabilizing	0.114	N	0.303	neutral	N	0.479821626	None	None	N
G/T	0.3721	ambiguous	0.3279	benign	-1.308	Destabilizing	0.938	D	0.644	neutral	None	None	None	None	N
G/V	0.5902	likely_pathogenic	0.5143	ambiguous	-0.554	Destabilizing	0.988	D	0.796	deleterious	N	0.511869709	None	None	N
G/W	0.8058	likely_pathogenic	0.7377	pathogenic	-1.595	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
G/Y	0.7607	likely_pathogenic	0.6817	pathogenic	-1.195	Destabilizing	1.0	D	0.809	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.