TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15691	47296;47297;47298	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
N2AB	14050	42373;42374;42375	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
N2A	13123	39592;39593;39594	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
N2B	6626	20101;20102;20103	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
Novex-1	6751	20476;20477;20478	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
Novex-2	6818	20677;20678;20679	chr2:178618387;178618386;178618385	chr2:179483114;179483113;179483112
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: Fn3-1
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1419
• 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/D	rs2057730753	None	0.999	N	0.843	0.393	0.450152462452	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/D	rs2057730753	None	0.999	N	0.843	0.393	0.450152462452	gnomAD-4.0.0	1.86063E-06	None	None	None	None	N	None	4.0093E-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
G/A	0.2357	likely_benign	0.2492	benign	-0.706	Destabilizing	0.619	D	0.408	neutral	N	0.49264431	None	None	N
G/C	0.5039	ambiguous	0.4998	ambiguous	-0.893	Destabilizing	1.0	D	0.916	deleterious	D	0.582701376	None	None	N
G/D	0.8121	likely_pathogenic	0.8162	pathogenic	-1.351	Destabilizing	0.999	D	0.843	deleterious	N	0.478259696	None	None	N
G/E	0.8579	likely_pathogenic	0.8334	pathogenic	-1.328	Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
G/F	0.9319	likely_pathogenic	0.9329	pathogenic	-0.805	Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
G/H	0.8664	likely_pathogenic	0.8727	pathogenic	-1.414	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
G/I	0.9355	likely_pathogenic	0.9318	pathogenic	-0.117	Destabilizing	0.999	D	0.929	deleterious	None	None	None	None	N
G/K	0.9662	likely_pathogenic	0.9544	pathogenic	-1.068	Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	N
G/L	0.9077	likely_pathogenic	0.9141	pathogenic	-0.117	Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	N
G/M	0.9279	likely_pathogenic	0.9331	pathogenic	-0.276	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
G/N	0.7145	likely_pathogenic	0.75	pathogenic	-0.926	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
G/P	0.9976	likely_pathogenic	0.9972	pathogenic	-0.272	Destabilizing	0.999	D	0.915	deleterious	None	None	None	None	N
G/Q	0.856	likely_pathogenic	0.8485	pathogenic	-1.0	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
G/R	0.8973	likely_pathogenic	0.8809	pathogenic	-0.943	Destabilizing	0.999	D	0.917	deleterious	D	0.536232097	None	None	N
G/S	0.1672	likely_benign	0.2134	benign	-1.227	Destabilizing	0.984	D	0.557	neutral	N	0.481242971	None	None	N
G/T	0.5653	likely_pathogenic	0.5438	ambiguous	-1.121	Destabilizing	0.998	D	0.89	deleterious	None	None	None	None	N
G/V	0.8534	likely_pathogenic	0.8427	pathogenic	-0.272	Destabilizing	0.998	D	0.887	deleterious	D	0.703857738	None	None	N
G/W	0.8783	likely_pathogenic	0.8927	pathogenic	-1.302	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/Y	0.8637	likely_pathogenic	0.8668	pathogenic	-0.81	Destabilizing	1.0	D	0.921	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.