TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32264	97015;97016;97017	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
N2AB	30623	92092;92093;92094	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
N2A	29696	89311;89312;89313	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
N2B	23199	69820;69821;69822	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
Novex-1	23324	70195;70196;70197	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
Novex-2	23391	70396;70397;70398	chr2:178543183;178543182;178543181	chr2:179407910;179407909;179407908
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-123
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1318
• 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/I	None	None	0.004	N	0.203	0.106	0.412715890961	gnomAD-4.0.0	6.8424E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99522E-07	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	0.5264	ambiguous	0.5457	ambiguous	-1.925	Destabilizing	0.78	D	0.716	prob.delet.	N	0.508616886	None	None	N
V/C	0.8737	likely_pathogenic	0.8857	pathogenic	-1.74	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
V/D	0.9641	likely_pathogenic	0.9733	pathogenic	-2.267	Highly Destabilizing	0.995	D	0.857	deleterious	N	0.476682519	None	None	N
V/E	0.9259	likely_pathogenic	0.9356	pathogenic	-2.042	Highly Destabilizing	0.996	D	0.825	deleterious	None	None	None	None	N
V/F	0.4076	ambiguous	0.4345	ambiguous	-1.243	Destabilizing	0.968	D	0.808	deleterious	N	0.495036582	None	None	N
V/G	0.7958	likely_pathogenic	0.8221	pathogenic	-2.483	Highly Destabilizing	0.995	D	0.81	deleterious	D	0.528299486	None	None	N
V/H	0.96	likely_pathogenic	0.9671	pathogenic	-2.3	Highly Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/I	0.075	likely_benign	0.0752	benign	-0.374	Destabilizing	0.004	N	0.203	neutral	N	0.459897432	None	None	N
V/K	0.9452	likely_pathogenic	0.9526	pathogenic	-1.621	Destabilizing	0.988	D	0.829	deleterious	None	None	None	None	N
V/L	0.2854	likely_benign	0.2944	benign	-0.374	Destabilizing	0.437	N	0.407	neutral	N	0.461817442	None	None	N
V/M	0.2915	likely_benign	0.3057	benign	-0.513	Destabilizing	0.976	D	0.732	prob.delet.	None	None	None	None	N
V/N	0.9055	likely_pathogenic	0.9292	pathogenic	-1.951	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
V/P	0.946	likely_pathogenic	0.9578	pathogenic	-0.862	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
V/Q	0.9182	likely_pathogenic	0.9305	pathogenic	-1.75	Destabilizing	0.996	D	0.83	deleterious	None	None	None	None	N
V/R	0.9173	likely_pathogenic	0.9312	pathogenic	-1.57	Destabilizing	0.996	D	0.858	deleterious	None	None	None	None	N
V/S	0.8008	likely_pathogenic	0.8283	pathogenic	-2.626	Highly Destabilizing	0.988	D	0.797	deleterious	None	None	None	None	N
V/T	0.7082	likely_pathogenic	0.7357	pathogenic	-2.229	Highly Destabilizing	0.919	D	0.724	prob.delet.	None	None	None	None	N
V/W	0.9626	likely_pathogenic	0.9681	pathogenic	-1.698	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/Y	0.8665	likely_pathogenic	0.8897	pathogenic	-1.292	Destabilizing	0.996	D	0.811	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.