TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22718	68377;68378;68379	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
N2AB	21077	63454;63455;63456	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
N2A	20150	60673;60674;60675	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
N2B	13653	41182;41183;41184	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
Novex-1	13778	41557;41558;41559	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
Novex-2	13845	41758;41759;41760	chr2:178578878;178578877;178578876	chr2:179443605;179443604;179443603
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: Fn3-52
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0553
• 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/F	None	None	0.993	D	0.836	0.709	0.845016314037	gnomAD-4.0.0	6.84412E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99692E-07	0	0
V/I	None	None	0.117	N	0.316	0.229	0.534239989213	gnomAD-4.0.0	3.42206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49846E-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	0.8745	likely_pathogenic	0.8348	pathogenic	-2.372	Highly Destabilizing	0.977	D	0.644	neutral	D	0.526475148	None	None	N
V/C	0.9569	likely_pathogenic	0.9507	pathogenic	-1.813	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/D	0.9976	likely_pathogenic	0.9985	pathogenic	-3.43	Highly Destabilizing	0.999	D	0.899	deleterious	D	0.622518726	None	None	N
V/E	0.9939	likely_pathogenic	0.9959	pathogenic	-3.104	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
V/F	0.8989	likely_pathogenic	0.9079	pathogenic	-1.335	Destabilizing	0.993	D	0.836	deleterious	D	0.562683658	None	None	N
V/G	0.9281	likely_pathogenic	0.9352	pathogenic	-2.986	Highly Destabilizing	0.999	D	0.892	deleterious	D	0.622518726	None	None	N
V/H	0.9983	likely_pathogenic	0.9987	pathogenic	-2.905	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/I	0.0969	likely_benign	0.0888	benign	-0.579	Destabilizing	0.117	N	0.316	neutral	N	0.51103362	None	None	N
V/K	0.995	likely_pathogenic	0.9971	pathogenic	-1.947	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
V/L	0.6299	likely_pathogenic	0.6569	pathogenic	-0.579	Destabilizing	0.898	D	0.587	neutral	N	0.505631733	None	None	N
V/M	0.7813	likely_pathogenic	0.7955	pathogenic	-0.858	Destabilizing	0.995	D	0.794	deleterious	None	None	None	None	N
V/N	0.9926	likely_pathogenic	0.9948	pathogenic	-2.658	Highly Destabilizing	0.999	D	0.909	deleterious	None	None	None	None	N
V/P	0.9932	likely_pathogenic	0.9926	pathogenic	-1.159	Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
V/Q	0.9937	likely_pathogenic	0.9957	pathogenic	-2.29	Highly Destabilizing	0.999	D	0.91	deleterious	None	None	None	None	N
V/R	0.9904	likely_pathogenic	0.9938	pathogenic	-2.052	Highly Destabilizing	0.999	D	0.913	deleterious	None	None	None	None	N
V/S	0.9743	likely_pathogenic	0.9726	pathogenic	-3.153	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
V/T	0.9438	likely_pathogenic	0.9398	pathogenic	-2.668	Highly Destabilizing	0.983	D	0.719	prob.delet.	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9986	pathogenic	-1.935	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Y	0.9903	likely_pathogenic	0.9918	pathogenic	-1.605	Destabilizing	0.999	D	0.845	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.