TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21953	66082;66083;66084	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
N2AB	20312	61159;61160;61161	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
N2A	19385	58378;58379;58380	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
N2B	12888	38887;38888;38889	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
Novex-1	13013	39262;39263;39264	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
Novex-2	13080	39463;39464;39465	chr2:178582946;178582945;178582944	chr2:179447673;179447672;179447671
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: Ig-125
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.7052
• Predicted PPI site: I

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/L	None	None	0.997	D	0.775	0.652	0.731077714775	gnomAD-4.0.0	1.86225E-06	None	None	None	None	I	None	0	3.0756E-05	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	0.9717	likely_pathogenic	0.974	pathogenic	-2.04	Highly Destabilizing	0.999	D	0.775	deleterious	D	0.615732359	None	None	I
V/C	0.9915	likely_pathogenic	0.9925	pathogenic	-1.986	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
V/D	0.9987	likely_pathogenic	0.999	pathogenic	-2.954	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/E	0.9973	likely_pathogenic	0.9977	pathogenic	-2.839	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.616337772	None	None	I
V/F	0.9858	likely_pathogenic	0.9827	pathogenic	-1.371	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
V/G	0.9713	likely_pathogenic	0.9768	pathogenic	-2.439	Highly Destabilizing	1.0	D	0.783	deleterious	D	0.616337772	None	None	I
V/H	0.9994	likely_pathogenic	0.9994	pathogenic	-1.945	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
V/I	0.1807	likely_benign	0.1447	benign	-0.968	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	I
V/K	0.9983	likely_pathogenic	0.9983	pathogenic	-1.692	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
V/L	0.9632	likely_pathogenic	0.9515	pathogenic	-0.968	Destabilizing	0.997	D	0.775	deleterious	D	0.581675595	None	None	I
V/M	0.972	likely_pathogenic	0.9636	pathogenic	-1.174	Destabilizing	1.0	D	0.869	deleterious	D	0.599914803	None	None	I
V/N	0.9945	likely_pathogenic	0.9953	pathogenic	-1.901	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
V/P	0.9934	likely_pathogenic	0.9914	pathogenic	-1.298	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
V/Q	0.998	likely_pathogenic	0.9983	pathogenic	-1.956	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
V/R	0.9966	likely_pathogenic	0.9967	pathogenic	-1.299	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
V/S	0.9875	likely_pathogenic	0.9897	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/T	0.9733	likely_pathogenic	0.9754	pathogenic	-2.179	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	I
V/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.722	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
V/Y	0.9978	likely_pathogenic	0.9976	pathogenic	-1.411	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I

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.