TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6504	19735;19736;19737	chr2:178728314;178728313;178728312	chr2:179593041;179593040;179593039
N2AB	6187	18784;18785;18786	chr2:178728314;178728313;178728312	chr2:179593041;179593040;179593039
N2A	5260	16003;16004;16005	chr2:178728314;178728313;178728312	chr2:179593041;179593040;179593039
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-49
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1256
• 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/L	rs762156103	-0.398	0.031	D	0.459	0.418	0.305730143919	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
V/L	rs762156103	-0.398	0.031	D	0.459	0.418	0.305730143919	gnomAD-4.0.0	6.84548E-07	None	None	None	None	N	None	0	0	None	0	2.52372E-05	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	0.5255	ambiguous	0.5149	ambiguous	-1.942	Destabilizing	0.296	N	0.685	prob.neutral	N	0.519138602	None	None	N
V/C	0.9347	likely_pathogenic	0.9187	pathogenic	-2.004	Highly Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
V/D	0.9606	likely_pathogenic	0.9577	pathogenic	-2.033	Highly Destabilizing	0.906	D	0.858	deleterious	None	None	None	None	N
V/E	0.9215	likely_pathogenic	0.9169	pathogenic	-1.883	Destabilizing	0.879	D	0.834	deleterious	D	0.635680672	None	None	N
V/F	0.322	likely_benign	0.242	benign	-1.311	Destabilizing	0.826	D	0.809	deleterious	None	None	None	None	N
V/G	0.6395	likely_pathogenic	0.6118	pathogenic	-2.41	Highly Destabilizing	0.879	D	0.853	deleterious	D	0.590408565	None	None	N
V/H	0.9704	likely_pathogenic	0.9637	pathogenic	-1.983	Destabilizing	0.991	D	0.835	deleterious	None	None	None	None	N
V/I	0.1018	likely_benign	0.0966	benign	-0.674	Destabilizing	0.002	N	0.207	neutral	None	None	None	None	N
V/K	0.9532	likely_pathogenic	0.95	pathogenic	-1.512	Destabilizing	0.906	D	0.836	deleterious	None	None	None	None	N
V/L	0.3111	likely_benign	0.2934	benign	-0.674	Destabilizing	0.031	N	0.459	neutral	D	0.558178757	None	None	N
V/M	0.358	ambiguous	0.3423	ambiguous	-0.922	Destabilizing	0.782	D	0.725	prob.delet.	D	0.619257703	None	None	N
V/N	0.9232	likely_pathogenic	0.9206	pathogenic	-1.678	Destabilizing	0.967	D	0.848	deleterious	None	None	None	None	N
V/P	0.9325	likely_pathogenic	0.9344	pathogenic	-1.067	Destabilizing	0.967	D	0.819	deleterious	None	None	None	None	N
V/Q	0.9239	likely_pathogenic	0.9223	pathogenic	-1.642	Destabilizing	0.967	D	0.824	deleterious	None	None	None	None	N
V/R	0.925	likely_pathogenic	0.9162	pathogenic	-1.266	Destabilizing	0.906	D	0.847	deleterious	None	None	None	None	N
V/S	0.8088	likely_pathogenic	0.7961	pathogenic	-2.4	Highly Destabilizing	0.906	D	0.819	deleterious	None	None	None	None	N
V/T	0.7197	likely_pathogenic	0.7142	pathogenic	-2.104	Highly Destabilizing	0.575	D	0.692	prob.neutral	None	None	None	None	N
V/W	0.9581	likely_pathogenic	0.9292	pathogenic	-1.613	Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
V/Y	0.8377	likely_pathogenic	0.7611	pathogenic	-1.275	Destabilizing	0.906	D	0.784	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.