TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29790	89593;89594;89595	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
N2AB	28149	84670;84671;84672	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
N2A	27222	81889;81890;81891	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
N2B	20725	62398;62399;62400	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
Novex-1	20850	62773;62774;62775	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
Novex-2	20917	62974;62975;62976	chr2:178553637;178553636;178553635	chr2:179418364;179418363;179418362
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: Fn3-105
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.0866
• 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	rs775906983	-0.29	0.006	N	0.38	0.083	0.158396225186	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	2.22965E-04	None	3.27E-05	None	0	0	0
V/I	rs775906983	-0.29	0.006	N	0.38	0.083	0.158396225186	gnomAD-4.0.0	6.84184E-06	None	None	None	None	N	None	0	0	None	0	1.00801E-04	None	0	0	0	4.63736E-05	3.31301E-05

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	0.3673	ambiguous	0.3417	ambiguous	-1.709	Destabilizing	0.006	N	0.471	neutral	N	0.513051552	None	None	N
V/C	0.7371	likely_pathogenic	0.7629	pathogenic	-1.444	Destabilizing	0.985	D	0.714	prob.delet.	None	None	None	None	N
V/D	0.7521	likely_pathogenic	0.7639	pathogenic	-1.575	Destabilizing	0.864	D	0.779	deleterious	N	0.472201251	None	None	N
V/E	0.6438	likely_pathogenic	0.6694	pathogenic	-1.374	Destabilizing	0.894	D	0.707	prob.neutral	None	None	None	None	N
V/F	0.3683	ambiguous	0.3633	ambiguous	-0.983	Destabilizing	0.864	D	0.717	prob.delet.	N	0.476315854	None	None	N
V/G	0.3804	ambiguous	0.3876	ambiguous	-2.224	Highly Destabilizing	0.761	D	0.733	prob.delet.	N	0.477898829	None	None	N
V/H	0.853	likely_pathogenic	0.8759	pathogenic	-1.924	Destabilizing	0.995	D	0.777	deleterious	None	None	None	None	N
V/I	0.0914	likely_benign	0.0919	benign	-0.291	Destabilizing	0.006	N	0.38	neutral	N	0.471108929	None	None	N
V/K	0.7235	likely_pathogenic	0.7561	pathogenic	-1.087	Destabilizing	0.894	D	0.715	prob.delet.	None	None	None	None	N
V/L	0.3237	likely_benign	0.3013	benign	-0.291	Destabilizing	0.114	N	0.511	neutral	N	0.479496339	None	None	N
V/M	0.296	likely_benign	0.2785	benign	-0.57	Destabilizing	0.894	D	0.694	prob.neutral	None	None	None	None	N
V/N	0.5841	likely_pathogenic	0.5928	pathogenic	-1.296	Destabilizing	0.945	D	0.795	deleterious	None	None	None	None	N
V/P	0.7202	likely_pathogenic	0.712	pathogenic	-0.734	Destabilizing	0.945	D	0.72	prob.delet.	None	None	None	None	N
V/Q	0.6611	likely_pathogenic	0.7039	pathogenic	-1.147	Destabilizing	0.945	D	0.747	deleterious	None	None	None	None	N
V/R	0.6954	likely_pathogenic	0.7279	pathogenic	-1.076	Destabilizing	0.894	D	0.793	deleterious	None	None	None	None	N
V/S	0.4933	ambiguous	0.5045	ambiguous	-2.032	Highly Destabilizing	0.809	D	0.685	prob.neutral	None	None	None	None	N
V/T	0.412	ambiguous	0.4162	ambiguous	-1.677	Destabilizing	0.547	D	0.645	neutral	None	None	None	None	N
V/W	0.9088	likely_pathogenic	0.9147	pathogenic	-1.349	Destabilizing	0.995	D	0.739	prob.delet.	None	None	None	None	N
V/Y	0.7239	likely_pathogenic	0.7508	pathogenic	-0.952	Destabilizing	0.945	D	0.717	prob.delet.	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.