TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29579	88960;88961;88962	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
N2AB	27938	84037;84038;84039	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
N2A	27011	81256;81257;81258	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
N2B	20514	61765;61766;61767	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
Novex-1	20639	62140;62141;62142	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
Novex-2	20706	62341;62342;62343	chr2:178554612;178554611;178554610	chr2:179419339;179419338;179419337
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: Fn3-103
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.8653
• 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/A	rs777595903	-0.159	0.978	N	0.463	0.308	0.564541561611	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/A	rs777595903	-0.159	0.978	N	0.463	0.308	0.564541561611	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs777595903	-0.159	0.978	N	0.463	0.308	0.564541561611	gnomAD-4.0.0	2.56215E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78535E-06	0	0
V/D	None	None	0.999	N	0.637	0.529	0.728753902033	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8578E-06	0	0
V/F	rs879204059	None	0.999	N	0.523	0.291	0.652406804477	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/F	rs879204059	None	0.999	N	0.523	0.291	0.652406804477	gnomAD-4.0.0	6.57315E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47003E-05	0	0
V/I	rs879204059	None	0.768	N	0.356	0.173	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs879204059	None	0.768	N	0.356	0.173	None	gnomAD-4.0.0	9.91472E-06	None	None	None	None	I	None	1.33497E-05	0	None	0	0	None	0	0	1.27135E-05	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	0.3968	ambiguous	0.3402	ambiguous	-0.524	Destabilizing	0.978	D	0.463	neutral	N	0.445271909	None	None	I
V/C	0.8894	likely_pathogenic	0.8658	pathogenic	-0.794	Destabilizing	1.0	D	0.569	neutral	None	None	None	None	I
V/D	0.7978	likely_pathogenic	0.74	pathogenic	-0.435	Destabilizing	0.999	D	0.637	neutral	N	0.424069918	None	None	I
V/E	0.7177	likely_pathogenic	0.6387	pathogenic	-0.516	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
V/F	0.3942	ambiguous	0.3363	benign	-0.65	Destabilizing	0.999	D	0.523	neutral	N	0.494353935	None	None	I
V/G	0.4881	ambiguous	0.4101	ambiguous	-0.655	Destabilizing	0.999	D	0.621	neutral	N	0.384239306	None	None	I
V/H	0.8863	likely_pathogenic	0.8408	pathogenic	-0.033	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
V/I	0.0877	likely_benign	0.0847	benign	-0.31	Destabilizing	0.768	D	0.356	neutral	N	0.458990568	None	None	I
V/K	0.7921	likely_pathogenic	0.7076	pathogenic	-0.518	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
V/L	0.2819	likely_benign	0.2004	benign	-0.31	Destabilizing	0.958	D	0.495	neutral	N	0.386282321	None	None	I
V/M	0.2387	likely_benign	0.198	benign	-0.614	Destabilizing	0.998	D	0.545	neutral	None	None	None	None	I
V/N	0.6526	likely_pathogenic	0.5704	pathogenic	-0.38	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
V/P	0.7164	likely_pathogenic	0.648	pathogenic	-0.35	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	I
V/Q	0.7121	likely_pathogenic	0.6258	pathogenic	-0.568	Destabilizing	0.999	D	0.592	neutral	None	None	None	None	I
V/R	0.7345	likely_pathogenic	0.6551	pathogenic	-0.01	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	I
V/S	0.5503	ambiguous	0.4798	ambiguous	-0.725	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	I
V/T	0.4292	ambiguous	0.3655	ambiguous	-0.704	Destabilizing	0.992	D	0.457	neutral	None	None	None	None	I
V/W	0.9401	likely_pathogenic	0.9216	pathogenic	-0.719	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
V/Y	0.8184	likely_pathogenic	0.7687	pathogenic	-0.446	Destabilizing	0.999	D	0.548	neutral	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.