TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27579	82960;82961;82962	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
N2AB	25938	78037;78038;78039	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
N2A	25011	75256;75257;75258	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
N2B	18514	55765;55766;55767	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
Novex-1	18639	56140;56141;56142	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
Novex-2	18706	56341;56342;56343	chr2:178563397;178563396;178563395	chr2:179428124;179428123;179428122
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-89
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3218
• 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/M	None	None	0.988	N	0.724	0.434	0.484109215787	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85853E-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
V/A	0.4008	ambiguous	0.3833	ambiguous	-1.391	Destabilizing	0.958	D	0.545	neutral	N	0.498645034	None	None	N
V/C	0.8709	likely_pathogenic	0.8643	pathogenic	-1.169	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/D	0.9466	likely_pathogenic	0.9156	pathogenic	-0.782	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
V/E	0.8564	likely_pathogenic	0.8167	pathogenic	-0.765	Destabilizing	0.994	D	0.796	deleterious	D	0.525639686	None	None	N
V/F	0.569	likely_pathogenic	0.5164	ambiguous	-1.03	Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
V/G	0.6669	likely_pathogenic	0.5885	pathogenic	-1.726	Destabilizing	0.994	D	0.778	deleterious	D	0.535982034	None	None	N
V/H	0.9573	likely_pathogenic	0.9439	pathogenic	-1.121	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/I	0.0803	likely_benign	0.0899	benign	-0.573	Destabilizing	0.862	D	0.548	neutral	None	None	None	None	N
V/K	0.9062	likely_pathogenic	0.8756	pathogenic	-1.09	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
V/L	0.4338	ambiguous	0.3991	ambiguous	-0.573	Destabilizing	0.067	N	0.257	neutral	N	0.479285731	None	None	N
V/M	0.3619	ambiguous	0.3377	benign	-0.574	Destabilizing	0.988	D	0.724	prob.delet.	N	0.513104839	None	None	N
V/N	0.8595	likely_pathogenic	0.8286	pathogenic	-0.946	Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
V/P	0.6844	likely_pathogenic	0.6491	pathogenic	-0.81	Destabilizing	0.998	D	0.828	deleterious	None	None	None	None	N
V/Q	0.8774	likely_pathogenic	0.8448	pathogenic	-1.052	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
V/R	0.9041	likely_pathogenic	0.8686	pathogenic	-0.626	Destabilizing	0.995	D	0.835	deleterious	None	None	None	None	N
V/S	0.7309	likely_pathogenic	0.6953	pathogenic	-1.571	Destabilizing	0.995	D	0.777	deleterious	None	None	None	None	N
V/T	0.6066	likely_pathogenic	0.5963	pathogenic	-1.42	Destabilizing	0.968	D	0.626	neutral	None	None	None	None	N
V/W	0.9746	likely_pathogenic	0.9655	pathogenic	-1.163	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Y	0.9002	likely_pathogenic	0.8632	pathogenic	-0.871	Destabilizing	0.995	D	0.823	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.