TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29410	88453;88454;88455	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
N2AB	27769	83530;83531;83532	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
N2A	26842	80749;80750;80751	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
N2B	20345	61258;61259;61260	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
Novex-1	20470	61633;61634;61635	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
Novex-2	20537	61834;61835;61836	chr2:178556926;178556925;178556924	chr2:179421653;179421652;179421651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-102
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.1033
• 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
V/A	None	None	0.999	D	0.669	0.798	0.803732359025	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
V/A	0.7877	likely_pathogenic	0.7399	pathogenic	-2.41	Highly Destabilizing	0.999	D	0.669	neutral	D	0.56992536	None	None	N
V/C	0.948	likely_pathogenic	0.9379	pathogenic	-1.592	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9969	pathogenic	-3.352	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.658039918	None	None	N
V/E	0.9949	likely_pathogenic	0.9933	pathogenic	-3.028	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/F	0.9056	likely_pathogenic	0.8702	pathogenic	-1.39	Destabilizing	1.0	D	0.866	deleterious	D	0.587865031	None	None	N
V/G	0.917	likely_pathogenic	0.8942	pathogenic	-2.999	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.658039918	None	None	N
V/H	0.9983	likely_pathogenic	0.9975	pathogenic	-2.903	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.1031	likely_benign	0.0963	benign	-0.678	Destabilizing	0.997	D	0.639	neutral	N	0.52046118	None	None	N
V/K	0.9967	likely_pathogenic	0.9961	pathogenic	-1.904	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/L	0.7018	likely_pathogenic	0.6208	pathogenic	-0.678	Destabilizing	0.997	D	0.691	prob.neutral	D	0.524888077	None	None	N
V/M	0.7945	likely_pathogenic	0.734	pathogenic	-0.907	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/N	0.9898	likely_pathogenic	0.9873	pathogenic	-2.638	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
V/P	0.9927	likely_pathogenic	0.9906	pathogenic	-1.241	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
V/Q	0.9935	likely_pathogenic	0.9916	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
V/R	0.9912	likely_pathogenic	0.9898	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
V/S	0.9489	likely_pathogenic	0.9346	pathogenic	-3.066	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/T	0.9081	likely_pathogenic	0.8821	pathogenic	-2.589	Highly Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
V/W	0.999	likely_pathogenic	0.9983	pathogenic	-1.913	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Y	0.991	likely_pathogenic	0.9881	pathogenic	-1.641	Destabilizing	1.0	D	0.856	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.